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It is part of the ectodermal dysplasia disorders caused by heterozygous mutations in<jats:italic>TP63<\/jats:italic>gene. EEC patients present limb malformations, orofacial clefting, skin and skin\u2019s appendages defects, ocular abnormalities. The transcription factor p63, encoded by<jats:italic>TP63<\/jats:italic>, is a master gene for the commitment of ectodermal-derived tissues, being expressed in the apical ectodermal ridge is critical for vertebrate limb formation and, at a later stage, for skin and skin\u2019s appendages development. The \u0394Np63<jats:italic>\u03b1<\/jats:italic>isoform is predominantly expressed in epithelial cells and it is indispensable for preserving the self-renewal capacity of adult stem cells and to engage specific epithelial differentiation programs. Small interfering RNA (siRNA) offers a potential therapy approach for EEC patients by selectively silencing the mutant allele. Here, using a systemic screening based on a dual-luciferase reported gene assay, we have successfully identified specific siRNAs for repressing the EEC-causing p63 mutant, R304W. Upon siRNA treatment, we were able to restore \u0394Np63-WT allele transcriptional function in induced pluripotent stem cells that were derived from EEC patient biopsy. This study demonstrates that siRNAs approach is promising and, may pave the way for curing\/delaying major symptoms, such as cornea degeneration and skin erosions in young EEC patients.<\/jats:p>","DOI":"10.1038\/cddis.2016.118","type":"journal-article","created":{"date-parts":[[2016,5,21]],"date-time":"2016-05-21T00:22:26Z","timestamp":1463790146000},"page":"e2227-e2227","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Allele-specific silencing of EEC p63 mutant R304W restores p63 transcriptional activity"],"prefix":"10.1038","volume":"7","author":[{"given":"F","family":"Novelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M","family":"Lena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Panatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Nasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Shalom-Feuerstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Candi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Melino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,19]]},"reference":[{"key":"BFcddis2016118_CR1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.4161\/cc.6.3.3796","volume":"6","author":"T Rinne","year":"2007","unstructured":"Rinne T, Brunner HG, van Bokhoven H . p63-associated disorders. 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