Systemic antisense therapeutics inhibiting DUX4 expression ameliorates FSHD-like pathology in an FSHD mouse model.

ABSTRACT: Aberrant expression of the double homeobox 4 (DUX4) gene in skeletal muscle causes muscle deterioration and weakness in Facioscapulohumeral muscular dystrophy (FSHD). Since the presence of a permissive pLAM1 polyadenylation signal is essential for stabilization of DUX4 mRNA and translation of DUX4 protein, disrupting the function of this structure can prevent expression of DUX4. We and others have shown promising results using antisense approaches to reduce DUX4 expression in vitro and in vivo following local intramuscular administration. Here we demonstrate that further development of the antisense chemistries enhances in vitro antisense efficacy. The optimal chemistry was conjugated to a cell-penetrating moiety and was systemically administered into the tamoxifen-inducible Cre-driver FLE

SUBMITTER: Lu-Nguyen N 

PROVIDER: S-EPMC8283208 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature