Therapeutic agent for glycogen storage disease type IA

A conjugate of an oligonucleotide and a GalNAc unit or a pharmacologically acceptable salt or solvate thereof, wherein the conjugate is selected from:

• 5′-Am1s-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Am1s-Te2s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1t-H-3′ (SEQ ID NO:
• 40) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 40,
• 5′-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Am1s-Te2s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2t—H-3′ (SEQ ID NO:
• 171) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 171,
• 5′-Um1s—Cm1s-Ce2s-Gm1s-Am1s-Te2s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2s—Um1t—H-3′ (SEQ ID NO:
• 172) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 172,
• 5′-Am1s-Am1s-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Am1s-Te2s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1t-H-3′ (SEQ ID NO:
• 42) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 42,
• 5′-Am1s-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Am1s-Te2s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2t—H-3′ (SEQ ID NO:
• 47) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 47,
• 5′-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Am1s-Te2s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2s—Um1t—H-3′ (SEQ ID NO:
• 48) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 48,
• 5′-Am1s-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1t-H-3′ (SEQ ID NO:
• 173) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 173,
• 5′-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2t—H-3′ (SEQ ID NO:
• 174) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 174,
• 5′-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2s—Um1t—H-3′ (SEQ ID NO:
• 175) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 175,
• 5′-Am1s-Am1s-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1t-H-3′ (SEQ ID NO:
• 176) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 176,
• 5′-Am1s-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2t—H-3′ (SEQ ID NO:
• 177) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 177,
• 5′-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2s—Um1t—H-3′ (SEQ ID NO:
• 178) and X18, wherein the X18 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 178,
• 5′-Am1s-Ae2s-Um1s—Cm1s—Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1t-H-3′ (SEQ ID NO:
• 173) and X20, wherein the X20 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 173,
• 5′-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1s-Ce2t—H-3′ (SEQ ID NO:
• 174) and X20, wherein the X20 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 174,
• 5′-Am1s-Am1s-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1t-H-3′ (SEQ ID NO:
• 176) and X20, wherein the X20 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 176, and
• 5′-Am1s-Ae2s-Um1s—Cm1s-Ce2s-Gm1s-Ae2s-Um1s-Gm1s-Gm1s-Ce2s-Gm1s-Am1s-Ae2s-Gm1sCe2t—H-3′ (SEQ ID NO:
• 177) and X20, wherein the X20 is a GalNAc unit attached to the 5′ end of SEQ ID NO:
• 177,
• wherein Gm1t, Um1t, Am1s, Gm1s, Cm1s, Um1s, Ce2t, Ae2s, Ce2s, Te2s, X18 and X20 are defined as follows:
• wherein the atomic bonding to phosphate group in X18 and X20 comprises formation of a phosphodiester bond by binding to the carbon atom at the 5′ end of the oligonucleotide.