Tetragalnac containing conjugates and methods for delivery of oligonucleotides

摘要

Disclosed herein is a modular composition comprising 1) an oligonucleotide; 2) one or more tetraGalNAc ligands of Formula (I), which may be the same or different; optionally, 3) one or more linkers, which may be the same or different; and optionally, 4) one or more targeting ligands, solubilizing agents, pharmacokinetics enhancing agents, lipids, and/or masking agents.

主权项

1. A modular composition comprising
1) a single stranded or double stranded oligonucleotide; 2) one or more tetraGalNAc ligands of Formula (I), (II) or (III), which may be the same or different: optionally, 3) one or more linkers, which may be the same or different; and optionally, 4) one or more targeting ligands, solubilizing agents, pharmacokinetics enhancing agents, lipids, and/or masking agents, wherein X is —O—, —S—, —CR1R2—or —NR1—, wherein R1 and R2 are each independently selected from the group consisting of hydrogen and C1-C6 alkyl; n is 1 , 2, 3, or 4; and the bond with “” indicates the point of attachment of the tetraGalNAc ligands to the oligonucleotide, either directly or through one or more optionally present linkers.