Modulation of enhancer RNA mediated gene expression
AssigneesIonis Pharmaceuticals, Inc., The Regents of the University of California
InventorsSusan M. Freier, Christopher K. Glass, Michael G. Rosenfeld, Wenbo Li, Michael T. Lam
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Abstract
Disclosed herein are methods and compounds for inhibiting gene expression by inhibiting enhancer RNAs (eRNAs). Such methods and compounds are useful for reducing expression of certain genes, many of which are associated with a variety of diseases and disorders.
Claims10
A method of inhibiting MMP9 gene expression in a mammalian cell comprising contacting the mammalian cell with a single-stranded antisense compound consisting of the sequence of SEQ ID NO:
- 3, wherein the antisense compound comprises:
- a gap segment consisting of linked deoxynucleosides;
- a 5′ wing segment consisting of linked nucleosides;
- and
- a 3′ wing segment consisting of linked nucleosides;
- wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a modified sugar, wherein the antisense compound targets an enhancer RNA (eRNA) transcribed from a genomic enhancer sequence or region, wherein the eRNA is an MMP9 eRNA sequence comprising the nucleic acid sequence of SEQ ID NO:
- 1, thereby inhibiting expression of the MMP9 gene in the mammalian cell.
A compound comprising a single-stranded antisense compound consisting of the sequence of SEQ ID NO:
- 3, wherein the antisense compound comprises:
- a gap segment consisting of linked deoxynucleosides;
- a 5′ wing segment consisting of linked nucleosides;
- and
- a 3′ wing segment consisting of linked nucleosides;
- wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a modified sugar, targeting an enhancer RNA (eRNA) transcribed from a genomic enhancer sequence or region, wherein the eRNA is an MMP9 eRNA sequence comprising the nucleic acid sequence of SEQ ID NO:1.
Dependencies are inferred from the claim text.