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Radical repair of these gene deficits via genome engineering is hardly feasible. The same applies to therapeutic stimulation of the spared allele by artificial transactivators. Small activating RNAs (saRNAs) offer an alternative, appealing approach. As a proof-of-principle, here we tested this approach on the Rett syndrome-linked, haploinsufficient,<jats:italic>Foxg1<\/jats:italic>brain patterning gene. We selected a set of artificial small activating RNAs (saRNAs) upregulating it in neocortical precursors and their derivatives. Expression of these effectors achieved a robust biological outcome. saRNA-driven activation (RNAa) was limited to neural cells which normally express<jats:italic>Foxg1<\/jats:italic>and did not hide endogenous gene tuning. saRNAs recognized target chromatin through a ncRNA stemming from it. Gene upregulation required Ago1 and was associated to RNApolII enrichment throughout the<jats:italic>Foxg1<\/jats:italic>locus. Finally, saRNA delivery to murine neonatal brain replicated<jats:italic>Foxg1<\/jats:italic>-RNAa<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/srep39311","type":"journal-article","created":{"date-parts":[[2016,12,20]],"date-time":"2016-12-20T10:47:44Z","timestamp":1482230864000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["RNA activation of haploinsufficient Foxg1 gene in murine neocortex"],"prefix":"10.1038","volume":"6","author":[{"given":"Cristina","family":"Fimiani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Goina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangping","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Mallamaci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,20]]},"reference":[{"key":"BFsrep39311_CR1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1750-1172-8-3","volume":"8","author":"T Bar\u00f8y","year":"2013","unstructured":"Bar\u00f8y, T. et al. Haploinsufficiency of two histone modifier genes on 6p22.3, ATXN1 and JARID2, is associated with intellectual disability. Orphanet Journal of Rare Diseases 8, 3 (2013).","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"BFsrep39311_CR2","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.gde.2013.03.004","volume":"23","author":"GL Carvill","year":"2013","unstructured":"Carvill, G. L. & Mefford, H. C. Microdeletion syndromes. Current Opinion in Genetics & Development 23, 232\u2013239 (2013).","journal-title":"Current Opinion in Genetics & Development"},{"key":"BFsrep39311_CR3","doi-asserted-by":"crossref","first-page":"e1005226","DOI":"10.1371\/journal.pgen.1005226","volume":"11","author":"D Lal","year":"2015","unstructured":"Lal, D. et al. Burden Analysis of Rare Microdeletions Suggests a Strong Impact of Neurodevelopmental Genes in Genetic Generalised Epilepsies. 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