Facioscapulohumeral muscular dystrophy (FSHD) is among the most prevalent muscular dystrophies, affecting over 830,000 people worldwide. FSHD is an autosomal dominant or digenic disorder caused by de-repression of the toxic <i>DUX4</i> gene in skeletal muscle. Currently no treatment exists that alters the course of FSHD, and therapy development remains an unmet need in the field. We propose that the most direct route to FSHD therapy will involve <i>DUX4</i> inhibition. Numerous labs in the FSHD field, including ours, are developing various strategies to inhibit <i>DUX4</i> using different mechanisms. Here we describe an approach to silence <i>DUX4</i> mRNA using new CRISPR/Cas13-based RNA editing strategy. Cas13 was originally developed as a RNA-guided CRISPR enzyme that cleaves RNA and not DNA. In addition, modified Cas13 can also be employed to precisely edit single bases on mRNAs. To do this, Cas13 is fused to a modified ADAR2 sequence (Adenosine Deaminase Acting on RNA) to produce a fusion protein that can direct cytidine-to-uridine editing on target mRNAs (C-to-U). Using this approach, glutamine codons can be edited to stop codons (CAA, CAG to UAA, UAG), thereby producing truncated, potentially non-toxic <i>DUX4</i> open reading frames. This precision editing requires the use of guide RNAs. Because this technology is new, guide RNA design still requires optimization. Here we developed a high-throughput dual-luciferase reporter system to test Cas13/ADAR-mediated RNA editing of <i>DUX4</i> mRNAs. Our strategy involved developing complex stable cell lines expressing reporter genes, Cas13/ADAR, and a transcriptionally active but non-toxic <i>DUX4</i> ORF. We cloned 240 different guide RNA expression constructs targeting 34 DUX4 glutamine codons, with the goal of editing glutamines to STOP codons. We expect to report results of <i>DUX4</i> mRNA editing efficiency and uncover better "rules" for designing effective RNA-editing gRNAs.