Current Gene Therapy

Ignacio Anegon
Director INSERM UMR 1064-Center for Research in Transplantation and Immunology
CHU de Nantes. 30, boulevard
Nantes
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Promotion of Cortico-Cerebral Precursors Expansion by Artificial pri-miRNAs Targeted Against the Emx2 Locus

Author(s): Assunta Diodato, Moira Pinzan, Marilena Granzotto, Antonello Mallamaci.

Abstract:

Emx2 encodes for a transcription factor controlling several aspects of cerebral cortex development. Its overexpression promotes self-renewal of young cortico-cerebral precursors, it promotes neuronal rather than gliogenic fates and it protects neuronal progenitors from cell death. These are all key activities for purposes of gene-promoted brain repair.

Artificial pri-miRNAs targeting non-coding cis-active modules and/or conserved sequences of the Emx2 locus were delivered to embryonic cortico-cerebral precursors, by lentiviral vectors. A subset of these pri-miRNAs upregulated Emx2, possibly stimulating its transcription. That led to enhanced self-renewal, delayed differentiation and reduced death of neuronally committed precursors, resulting in an appreciable expansion of the neuronogenic precursors pool. This method makes Emx2 overexpression for purposes of brain repair a more feasible goal, avoiding the drawbacks of exogenous gene copies introduction.

Interestingly, the two genomic enhancers targeted by these pri-miRNAs were discovered to be naturally transcribed. Their expression profile suggests their possible involvement in regulation of Emx2 transcription.

Keywords: Emx2, cerebral cortex, RNAa, neural stem cell, neuronal progenitor, lentivector

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Article Details

VOLUME: 13
ISSUE: 2
Year: 2013
Page: [152 - 161]
Pages: 10
DOI: 10.2174/1566523211313020009
Price: $58