RNA activation of haploinsufficient Foxg1 gene in murine neocortex
UMass Chan AffiliationsHorae Gene Therapy Center
Department of Microbiology and Physiological Systems
Viral Vector Core
Document TypeJournal Article
Genetics and Genomics
Nervous System Diseases
Neuroscience and Neurobiology
MetadataShow full item record
AbstractMore 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.
SourceSci Rep. 2016 Dec 20;6:39311. doi: 10.1038/srep39311. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40224
Related ResourcesLink to Article in PubMed
RightsCopyright © 2016, The Author(s).