| abstract |
RNA interference-based products and methods for inhibiting the expression of the double homeobox 4 (DUX4) gene on human chromosome 4q35 are disclosed. The disclosure includes the Cas13 protein silencing of RNA, wherein Cas13 is specifically targeted to a DUX4 region of interest using a sequence- specific guide RNA (gRNA). Recombinant adeno-associated viruses of the disclosure deliver DNAs encoding inhibitory gRNAs that are constructed with Cas13 direct repeats to knock down the expression of DUX4. The methods have application in the treatment of muscular dystrophies including, but not limited to, facioscapulohumeral muscular dystrophy (FSHD), and other disorders associated with elevated DUX4 expression, including cancer. |