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Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in <jats:italic>in vitro<\/jats:italic> systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest <jats:italic>in vivo<\/jats:italic>. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied <jats:italic>in vivo<\/jats:italic> as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins.<\/jats:p>","DOI":"10.1038\/srep27315","type":"journal-article","created":{"date-parts":[[2016,6,6]],"date-time":"2016-06-06T09:13:41Z","timestamp":1465204421000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo"],"prefix":"10.1038","volume":"6","author":[{"given":"Alessia","family":"Indrieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Grimaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Zucchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Tammaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Gustincich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunella","family":"Franco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,6]]},"reference":[{"key":"BFsrep27315_CR1","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nbt.2158","volume":"30","author":"F Modarresi","year":"2012","unstructured":"Modarresi, F. et al. 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S.G. and S.Z. are named inventors in patent issued in the US Patent and Trademark Office on SINEUPs and licensed to TransSINE Technologies. A.I., C.G., R.T. and B.F. declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27315"}}