Abstract: RNA interference-based products and methods for inhibiting the expression of a mutant myelin protein zero (MPZ) gene in a cell or in the cells of a subject are disclosed. The disclosure includes microRNA that specifically target various regions of the MPZ gene to knock down expression of the aberrant protein. Additionally, the disclosure includes delivery of a nucleic acid encoding normal, wild-type, or functionally active MPZ protein. Additionally, the disclosure includes recombinant adeno-associated viruses to deliver nucleic acids encoding the microRNAs to knock down the expression of aberrant MPZ protein and/or to deliver nucleic acids encoding normal, wild-type, or functionally active MPZ protein. The disclosure includes methods of using these nucleic acids in the treatment of diseases associated with MPZ gene mutations including, but not limited to, Charcot-Marie-Tooth disease type 1B (CMT 1B) disease.

Abstract: Disclosed herein are products, methods, and uses for treating, ameliorating, udaying the progression of, and/or preventing a muscular dystrophy or a cancer including, but not limited to, facioscapulohumeral muscular dystrophy (FSHD) or a sarcoma. More particularly, disclosed herein are RNA interference-based products, methods, and uses for inhibiting or downregulating the expression of double homeobox 4 (DUX4). Even more particularly, the disclosure provides nucleic acids comprising U7 DUX4 antisense sequences for inhibiting or downregulating the expression of DUX4 and methods of using said antisense sequences to inhibit or downregulate DUX4 expression in cells and/or in cells of a subject having a muscular dystrophy or a cancer including, but not limited to, FSHD or a cancer.

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.