UMMS Affiliation

Viral Vector Core; Department of Microbiology and Physiological Systems; Horae Gene Therapy Center

Publication Date


Document Type



Genetics and Genomics | Nervous System Diseases | Neuroscience and Neurobiology | Therapeutics


More than one hundred distinct gene hemizygosities are specifically linked to epilepsy, mental retardation, autism, schizophrenia and neuro-degeneration. 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, Foxg1 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 Foxg1 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 Foxg1 locus. Finally, saRNA delivery to murine neonatal brain replicated Foxg1-RNAa in vivo.


Epilepsy, Gene therapy, Molecular medicine, Small RNAs

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Copyright © 2016, The Author(s).

DOI of Published Version



Sci Rep. 2016 Dec 20;6:39311. doi: 10.1038/srep39311. Link to article on publisher's site

Journal/Book/Conference Title

Scientific reports

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Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.



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