This study evaluates the therapeutic potential of RNA interference (RNAi) targeting hepatic glycogen synthase 2 (Gys2) in mouse models of glycogen storage diseases (GSDs). Using GalNAc-conjugated and lipid nanoparticle-formulated small interfering RNAs (siRNAs) to silence Gys2 expression, the researchers observed significant reductions in hepatic glycogen accumulation, hepatomegaly, fibrosis, and nodule development in GSD III (Agl⁻/⁻) mice. Additionally, in a GSD Ia (L-G6pc⁻/⁻) mouse model, Gys2 silencing led to decreased glycogen and lipid accumulation, reduced liver enzyme levels, and ameliorated liver pathology. These findings suggest that hepatic Gys2 inhibition via RNAi could be a viable therapeutic strategy to prevent liver complications associated with hepatic GSDs.
RNAi-mediated silencing of Gys2 effectively reduces hepatic glycogen and lipid accumulation, preventing liver injury and fibrosis in mouse models of GSD III and GSD Ia.
GSD III (Agl⁻/⁻) and GSD Ia (L-G6pc⁻/⁻) mouse models, developed by constitutive deletion of the Agl and liver-specific deletion of the G6pc genes, respectively, to mimic human GSD III and GSD Ia conditions.
Glycogen storage disease, Liver fibrosis, RNA interference, Glycogen metabolism, Hepatic steatosis
Constitutive Knockout models, Agl gene deletion, Liver-specific G6pc deletion, siRNA therapy, GalNAc and lipid nanoparticle delivery systems
From model design to experimental results
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