Compounds include at least one cyclic cell penetrating peptide (cCPP) conjugated to an antisense compound (AC). The AC modulates splicing of an RNA transcript. For example, the AC induces exon skipping. Exon skipping can result in down-regulation of expression or activity of a protein. Exon skipping may cause a frameshift in a resulting mRNA. The frameshift may result in a premature termination codon. The frameshift may result in nonsense mediated decay.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of GYS1 RNA in a cell or subject, and in certain instances reducing the amount of GYS1 protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a glycogen storage disease. Such glycogen storage diseases include Lafora disease, adult polyglucosan body disease (APBD), Andersen's disease, and Pompe disease.

This disclosure relates to oligonucleotides, compositions and methods useful for reducing GYS2 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of GYS2 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of GYS2 expression may also include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat glycogen storage diseases (e.g., GSDIa, GSDIII, GSDIV, GSDVI, and GSDIX) and related conditions.