Crispr-inhibition for facioscapulohumeral muscular dystrophy
AssigneeNevada Research & Innovation Corporation
InventorsPeter L. JONES, Charis L. HIMEDA
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Abstract
The disclosure relates to methods and compositions for inhibiting the expression of the DUX4 gene in skeletal muscle cells. In some aspects, the invention includes a CRISPR interference platform that directs an epigenetic regulator to the DUX4 locus. In some aspects, methods described by the disclosure are useful in modulating DUX4 expression for the treatment of facioscapulohumeral muscular dystrophy (FSHD).
Claims23
A polynucleotide comprising nucleic acid sequences encoding a CRISPR interference (CRISPRi) platform comprising a single guide RNA (sgRNA) and a fusion polypeptide,
- wherein the sgRNA is encoded by a nucleic acid sequence comprising (i) the nucleic acid sequence of any one of SEQ ID NOs:
- 38, 39, and 41-43 or (ii) 12 to 20 contiguous nucleotides of a nucleic acid sequence selected from any one of SEQ ID NOs:
- 38, 39, and 41-43, and
- wherein the fusion polypeptide further comprises a catalytically inactive Cas9 (dCas9 or iCas9) fused to an epigenetic repressor.
(canceled)
(canceled)
A vector comprising a polynucleotide comprising nucleic acid sequences encoding a CRISPRi platform comprising an sgRNA and a fusion polypeptide,
- wherein the sgRNA is encoded by a sequence comprising (i) the nucleic acid sequence of any one of SEQ ID NOs:
- 38, 39, and 41-43 or (ii) 12 to 20 contiguous nucleotides selected from the nucleic acid sequence of any one of SEQ ID NOs:
- 38, 39, and 41-43, and
- wherein the fusion polypeptide further comprises a catalytically inactive Cas9 (dCas9 or iCas9) fused to an epigenetic repressor.
14-18. (canceled)
20-30. (canceled)
A polynucleotide encoding a CRISPR interference (CRISPRi) platform comprising a single guide RNA (sgRNA) and a fusion polypeptide, wherein the fusion polypeptide comprises the amino acid sequence of SEQ ID NO:56.
Dependencies are inferred from the claim text.