申请人：Alnylam Pharmaceuticals, Inc.
公开号：US20160051691A1
公开（公告）日：2016-02-25
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(R
N
) 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 L
G
, -Linker-L
G
, or has the structure shown below:
L
G
is independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, polysaccharide;
R
N
is 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.
本发明提供了包含至少一个式(I)的亚单位的iRNA试剂：
其中：
A和B分别独立于每次出现O、N(RN)或S；
X和Y分别独立于每次出现H、OH、一个羟基保护基团、一个磷酸基团、一个磷酸二酯基团、一个活化磷酸基团、一个活化亚磷酸基团、一个磷酰胺基团、一个固相支持、-P(Z')(Z″)O-核苷、-P(Z')(Z″)O-寡核苷酸、一个脂质、一个PEG、一个类固醇、一个亲脂物质、一个聚合物、-P(Z')(Z″)O-连接子-OP(Z′″)(Z″″)O-寡核苷酸、一个核苷酸、一个寡核苷酸、-P(Z')(Z″)-式(I)、-P(Z')(Z″)-或-连接子-R；
R是LG、-连接子-LG，或具有下面所示结构：
LG独立于每次出现的是一种碳水化合物，例如，单糖、双糖、三糖、四糖、寡糖、多糖；
RN独立于每次出现的是H、甲基、乙基、丙基、异丙基、丁基或苄基；
Z'、Z″、Z′″和Z″″分别独立于每次出现的是O或S。
