Abstract: The disclosure relates to methods and compositions for regulating expression of DUX4. In some aspects, methods described by the disclosure are useful for treating a disease associated with aberrant DUX4 expression (e.g., facioscapulohumeral muscular dystrophy. FSHD).

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).

Abstract: The disclosure relates to methods and compositions for regulating expression of DUX4. Specifically, the disclosure provides a recombinant gene editing complex comprising: a recombinant gene editing protein; and, a nucleic acid encoding a guide RNA (gRNA) that specifically hybridizes to a target nucleic acid sequence encoding a D4Z4 macrosatellite repeat region, wherein binding of the complex to the target nucleic acid sequence results in inhibition of DUX4 gene expression. In some aspects, methods described by the disclosure are useful for treating a disease associated with aberrant DUX4 expression (e.g., facioscapulohumeral muscular dystrophy, FSHD).

Abstract: The disclosure relates to methods and compositions for regulating expression of DUX4. Specifically, the disclosure provides a recombinant gene editing complex comprising: a recombinant gene editing protein; and, a nucleic acid encoding a guide RNA (gRNA) that specifically hybridizes to a target nucleic acid sequence encoding a D4Z4 macrosatellite repeat region, wherein binding of the complex to the target nucleic acid sequence results in inhibition of DUX4 gene expression. In some aspects, methods described by the disclosure are useful for treating a disease associated with aberrant DUX4 expression (e.g., facioscapulohumeral muscular dystrophy, FSHD).