Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use

An siRNA, comprising a sense strand and an antisense strand, each nucleotide in the siRNA being independently a modified or unmodified nucleotide;

• wherein the sense strand comprises a nucleotide sequence I, and the antisense strand comprises a nucleotide sequence II;
• the nucleotide sequence I and the nucleotide sequence II are reverse complementary to form a double-stranded region;
• wherein the nucleotide sequence I comprises a nucleotide sequence represented by SEQ ID NO:
• 3, and the nucleotide sequence II comprises a nucleotide sequence represented by SEQ ID NO:
• 4;
• (SEQ ID NO:
• 3)
• 5′-CCUAUGAAGAUUAUAAGAZ3-3′;
• (SEQ ID NO:
• 4)
• 5′-Z4UCUUAUAAUCUUCAUAGG-3′,
• wherein Z3 is selected from A, U, G or C, and Z4 is the first nucleotide at the 5′ terminal of the antisense strand and complementary to Z3;
• or the nucleotide sequence I comprises a nucleotide sequence represented by SEQ ID NO:
• 63, and the nucleotide sequence II comprises a nucleotide sequence represented by SEQ ID NO:
• 64;
• (SEQ ID NO:
• 63)
• 5′-GUACAGUACCAGAAGUUAZ7-3′;
• (SEQ ID NO:
• 64)
• 5′-Z8UAACUUCUGGUACUGUAC-3′,
• wherein Z7 is selected from A, U, G or C, and Z8 is the first nucleotide at the 5′ terminal of the antisense strand and complementary to Z7;
• or the nucleotide sequence I comprises a nucleotide sequence represented by SEQ ID NO:
• 123, and the nucleotide sequence II comprises a nucleotide sequence represented by SEQ ID NO:
• 124;
• (SEQ ID NO:
• 123)
• 5′-CAAACAAGCUGCACAGAAZ11-3′;
• (SEQ ID NO:
• 124)
• 5′-Z12UUCUGUGCAGCUUGUUUG-3′,
• wherein Z11 is selected from A, U, G or C, and Z12 is the first nucleotide at the 5′ terminal of the antisense strand and complementary to Z11;
• or the nucleotide sequence I comprises a nucleotide sequence represented by SEQ ID NO:
• 183, and the nucleotide sequence II comprises a nucleotide sequence represented by SEQ ID NO:
• 184:
• (SEQ ID NO:
• 183)
• 5′-CAAACAAGGACUAAUCCAZ15-3′;
• (SEQ ID NO:
• 184)
• 5′-Z16UGGAUUAGUCCUUGUUUG-3′,
• wherein Z15 is selected from A, U, G or C, and Z16 is the first nucleotide at the 5′ terminal of the antisense strand and complementary to Z15.