Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5' end to 3' end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.本發明提供了一種雙鏈寡核苷酸，前述雙鏈寡核苷酸含有正義鏈和反義鏈，前述正義鏈包含核苷酸序列1，前述反義鏈包含核苷酸序列2，前述核苷酸序列1和前述核苷酸序列2的長度均為19個核苷酸，按照5'末端到3'末端的方向，前述核苷酸序列1的第7、8、9位的核苷酸為氟代修飾的核苷酸，前述核苷酸序列2的第2、6、14、16位的核苷酸為氟代修飾的核苷酸，前述核苷酸序列1和2的其他位置的每個核苷酸獨立地為非氟代修飾的核苷酸中的一種。本發明還提供了包含該雙鏈寡核苷酸的藥物組合物和綴合物。本發明的雙鏈寡核苷酸、藥物組合物和綴合物具有良好的調節基因表現的活性。
