Modulation of gene transcription using antisense oligonucleotides targeting regulatory RNAs

An antisense oligonucleotide (ASO) comprising MT=MG=M5C-MA-MG=dG=d5C=dA=d5C=dA=d5C-dA=d5C-dA=dT=M5C-MA-MG=MG=M5C-[TEG] (SEQ ID NO:

• 409), wherein MT, MG, MA, and M5C are 2′-O-methoxyethyl thymidine, 2′-O-methoxyethyl guanosine, 2′-O-methoxyethyl adenosine, and 2′-O-methoxyethyl 5-methyl cytidine ribonucleosides;
• dA, dG, dT, and d5C are 2′-deoxy adenosine, 2′-deoxy guanosine, 2′-deoxy thymidine and 2′-deoxy 5-methyl cytidine ribonucleosides, “=” is a phosphorothioate linkage, “-” is a phosphodiester linkage, and [TEG] is a ligand moiety comprising a triethyleneglycol linked to N-acetylgalactosamine (GalNAc).

An antisense oligonucleotide (ASO) comprising MT=MG=M5C-MA-MG-dG-d5C=dA=d5C=dA=d5C=dA=d5C=dA=dT=M5C-MA-MG-MG=M5C (SEQ ID NO:

• 404), wherein MT, MG, MA, and M5C are 2′-O-methoxyethyl thymidine, 2′-O-methoxyethyl guanosine, 2′-O-methoxyethyl adenosine, and 2′-O-methoxyethyl 5-methyl cytidine ribonucleosides;
• dA, dG, dT, and d5C are 2′-deoxy adenosine, 2′-deoxy guanosine, 2′-deoxy thymidine and 2′-deoxy 5-methyl cytidine ribonucleosides, “=” is a phosphorothioate linkage, and “-” is a phosphodiester linkage.