{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:05:03Z","timestamp":1773270303791,"version":"3.50.1"},"publisher-location":"New York, NY","reference-count":4,"publisher":"Springer US","isbn-type":[{"value":"9781071620090","type":"print"},{"value":"9781071620106","type":"electronic"}],"license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The genodermatosis dystrophic epidermolysis bullosa (DEB) is caused by mutations in the <jats:italic>COL7A1<\/jats:italic> gene which encodes type VII collagen (C7). In the cutaneous basement membrane zone, C7 secures attachment of the epidermal basal keratinocyte to the papillary dermis by means of anchoring fibril formation. The complete absence of these anchoring fibrils leads to severe blistering of skin and mucosa upon the slightest friction and early mortality. To date, although preclinical advances toward therapy are promising, treatment for the disease is merely symptomatic. Therefore, research into novel therapeutics is warranted.<\/jats:p><jats:p>Antisense oligonucleotide (ASO)-mediated exon skipping is such a therapy. Clinical examination of naturally occurring exon skipping suggested that this mechanism could most likely benefit the most severely affected patients. The severe form of DEB is caused by biallelic null mutations. Exon skipping aims to bind an ASO to the mutated exon of the pre-mRNA in the cell nucleus. Thereby, the ASO inhibits the recognition of the mutated exon by the splicing machinery, and as a result, the mutated exon is spliced out from the mRNA with its surrounding introns, i.e., it is skipped. Here, we describe in vitro methods to evaluate ASO-mediated exon skipping in a preclinical setting.<\/jats:p>","DOI":"10.1007\/978-1-0716-2010-6_11","type":"book-chapter","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T11:11:35Z","timestamp":1645787495000},"page":"185-190","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Vitro Models for the Evaluation of Antisense Oligonucleotides in Skin"],"prefix":"10.1007","author":[{"given":"Jeroen","family":"Bremer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C.","family":"van den Akker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"issue":"4","key":"11_CR1","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1111\/bjd.18921","volume":"183","author":"C Has","year":"2020","unstructured":"Has C, Bauer JW, Bodemer C, Bolling MC, Bruckner-Tuderman L, Diem A, Fine JD, Heagerty A, Hovnanian A, Marinkovich MP, Martinez AE, McGrath JA, Moss C, Murrell DF, Palisson F, Schwieger-Briel A, Sprecher E, Tamai K, Uitto J, Woodley DT, Zambruno G, Mellerio JE (2020) Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol 183(4):614\u2013627. https:\/\/doi.org\/10.1111\/bjd.18921","journal-title":"Br J Dermatol"},{"key":"11_CR2","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.omtn.2019.09.009","volume":"18","author":"J Bremer","year":"2019","unstructured":"Bremer J, van der Heijden EH, Eichhorn DS, Meijer R, Lemmink HH, Scheffer H, Sinke RJ, Jonkman MF, Pasmooij AMG, Van den Akker PC (2019) Natural exon skipping sets the stage for exon skipping as therapy for dystrophic epidermolysis bullosa. Mol Ther Nucleic Acids 18:465\u2013475","journal-title":"Mol Ther Nucleic Acids"},{"issue":"3","key":"11_CR3","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/mt.2008.205","volume":"17","author":"A Aartsma-Rus","year":"2009","unstructured":"Aartsma-Rus A, van Vliet L, Hirschi M, Janson AA, Heemskerk H, de Winter CL, de Kimpe S, van Deutekom JC, t Hoen PA, van Ommen GJ (2009) Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms. Mol Ther 17(3):548\u2013553. https:\/\/doi.org\/10.1038\/mt.2008.205","journal-title":"Mol Ther"},{"issue":"7","key":"11_CR4","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1038\/mt.2016.92","volume":"24","author":"O Bornert","year":"2016","unstructured":"Bornert O, K\u00fchl T, Bremer J, van den Akker PC, Pasmooij AM, Nystr\u00f6m A (2016) Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy. Mol Ther 24(7):1302\u20131311. https:\/\/doi.org\/10.1038\/mt.2016.92","journal-title":"Mol Ther"}],"container-title":["Methods in Molecular Biology","Antisense RNA Design, Delivery, and Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/978-1-0716-2010-6_11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:32:44Z","timestamp":1650587564000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/978-1-0716-2010-6_11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"ISBN":["9781071620090","9781071620106"],"references-count":4,"URL":"https:\/\/doi.org\/10.1007\/978-1-0716-2010-6_11","relation":{},"ISSN":["1064-3745","1940-6029"],"issn-type":[{"value":"1064-3745","type":"print"},{"value":"1940-6029","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]},"assertion":[{"value":"25 February 2022","order":1,"name":"first_online","label":"First Online","group":{"name":"ChapterHistory","label":"Chapter History"}}]}}