TABLE 2.
Summary of results from pre-clinical studies on RNA interference for DUX4 knockdown.
| Study | Approach | DUX4 target | Model | DUX4 knockdown (dose) | Other results |
|---|---|---|---|---|---|
| Vanderplanck et al. (2011) | siRNA | Ex2 SA, Ex3 SA | Primary FSHD myoblasts, differentiated post-treatment | 80% (ex3 SA, 10 nM) | Reduced DUX4, Atrogin1, TP53, protein levels, and MuRF1+ nuclei; improved muscle size |
| Wallace et al. (2012) | miRNA | Ex1 | DUX4-luciferase reporter HEK293 cells | >50% (dose not given) | Reduced DUX4 protein levels |
| Ex1 | AAV-DUX4 mice, 1x i.m. TA, evaluated 2–4 weeks post-treatment | 64% (3 × 1010 particles) | Reduced DUX4 protein levels (90%); improved histopathology; lack of caspase-3+ myofibers; improved grip strength | ||
| Lim et al. (2015) | siRNA | Promoter, Ex1, In2, downstream elements | Primary FSHD myoblasts, differentiated post-treatment | Up to ∼50–90% (100 pmol) | Reduced DUX4+ nuclei, ZSCAN4 expression |
| Wallace et al. (2018) | miRNA | Ex1, Ex2, Ex3 | DUX4-luciferase reporter HEK293 cells | Up to >75% (dose not given) | Reduced DUX4 protein levels (up to >75%) |
| Ex1 | AAV-DUX4 mice, 1x i.m. TA/isolated limb perfusion, evaluated at various timepoints post-treatment | Not assessed | One miRNA was more toxic than the other upon histological evaluation |
siRNA, small interfering RNA; miRNA, microRNA; Ex, exon; In, intron; SA, splice acceptor; i.m., intramuscular injection; TA, tibialis anterior; AAV, adeno-associated virus.