Carbohydrate conjugates as delivery agents for oligonucleotides

摘要

The present invention provides iRNA agents comprising at least one subunit of the formula (I):;wherein:A and B are each independently for each occurrence O, N(RN) or S;X and Y are each independently for each occurrence H, OH, a hydroxyl protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z′)(Z″)O-Linker-OP(Z′″)(Z″)O-oligonucleotide, a nucleotide, an oligonucleotide, —P(Z′)(Z″)-formula (I), —P(Z′)(Z″)- or -Linker-R;
R is LG, -Linker-LG, or has the structure shown below:;LG is independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, polysaccharide;RN is independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl; andZ′, Z″, Z′″ and Z″″ are each independently for each occurrence O or S.

主权项

1. A modified HBV-targeting oligonucleotide comprising a structure shown below: wherein LG is independently for each occurrence a ligand, and all of the nucleotide sugars of the oligonucleotide are modified; and wherein the oligonucleotide targets the HBV gene.