| 摘要 |
PROBLEM TO BE SOLVED: To provide new receptor specific ligand conjugated iRNA agents and methods for their preparation that address shortcomings of in vivo delivery of oligonucleotide therapeutics.SOLUTION: The present invention provides iRNA agents comprising at least one subunit of the formula (I). In the formula, A and B are each independently O, N(R) or S; X and Y are each independently for each occurrence H, OH, a hydroxy 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 Lor -Linker-L, or has the structure including a plurality of -Linker-Las branched chains shown in the chemical formula 7 herein, where Lis independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, or polysaccharide; Ris independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl; and Z', Z'', Z''' and Z'''' are each independently for each occurrence O or S.SELECTED DRAWING: None |
