{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:33:32Z","timestamp":1791286412113,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,10,28]],"date-time":"2011-10-28T00:00:00Z","timestamp":1319760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The vascular type of the Ehlers\u2010Danlos syndrome (vEDS) is caused by dominant\u2010negative mutations in the procollagen type III\n                    <jats:italic>(COL3A1)<\/jats:italic>\n                    gene. Patients with this autosomal dominant disorder have a shortened life expectancy due to complications from ruptured vessels or hollow organs. We tested the effectiveness of allele\u2010specific RNA interference (RNAi) to reduce the mutated phenotype in fibroblasts. Small\u2010interfering RNAs (siRNAs) discriminating between wild\u2010type and mutant\n                    <jats:italic>COL3A1<\/jats:italic>\n                    allele were identified by a luciferase reporter gene assay and in primary fibroblasts from a normal donor and a patient with vEDS. The best discriminative siRNA with the mutation at position 10 resulted in &gt;90% silencing of the mutant allele without affecting the wild\u2010type allele. Transmission and immunogold electron microscopy of extracted extracellular matrices from untreated fibroblasts of the patient with vEDS revealed structurally abnormal fibrils. After siRNA treatment, collagen fibrils became similar to fibrils from fibroblasts of normal and\n                    <jats:italic>COL3A1<\/jats:italic>\n                    haploinsufficient donors. In addition, it was shown that expression of mutated COL3A1 activates the unfolded protein response and that reduction of the amount of mutated protein by siRNA reduces cellular stress. Taken together, the results provide evidence that allele\u2010specific siRNAs are able to reduce negative effects of mutated COL3A1 proteins. Thus, the application of allele\u2010specific RNAi may be a promising direction for future personalized therapies to reduce the severity of vEDS.\u2014M\u00fcller, G. A., Hansen, U., Xu, Z., Griswold, B., Talan, M. I., McDonnell, N. B., Briest, W. Allele\u2010specific siRNA knockdown as a personalized treatment strategy for vascular Ehlers\u2010Danlos syndrome in human fibroblasts.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 668\u2013677 (2012). www.fasebj.org\n                  <\/jats:p>","DOI":"10.1096\/fj.11-182162","type":"journal-article","created":{"date-parts":[[2011,10,28]],"date-time":"2011-10-28T23:45:45Z","timestamp":1319845545000},"page":"668-677","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Allele\u2010specific siRNA knockdown as a personalized treatment strategy for vascular Ehlers\u2010Danlos syndrome in human fibroblasts"],"prefix":"10.1096","volume":"26","author":[{"given":"Gerd A.","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Sciences National Institute on Aging  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Hansen","sequence":"additional","affiliation":[{"name":"University Hospital of M\u00fcnster Institute of Physiological Chemistry and Pathobiochemistry  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation National Institute on Aging  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Griswold","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation National Institute on Aging  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark I.","family":"Talan","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Sciences National Institute on Aging  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazli B.","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation National Institute on Aging  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Briest","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Sciences National Institute on Aging  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,10,28]]},"reference":[{"key":"e_1_2_25_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O"},{"key":"e_1_2_25_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2007.12.005"},{"key":"e_1_2_25_4_1","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1172-2-32","article-title":"Ehlers\u2010Danlos syndrome type IV","volume":"2","author":"Germain D. 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