Sirnas for simultaneously inhibiting expression of two target genes, drug and use thereof

A dual-targeting siRNA agent, wherein the dual-targeting siRNA agent comprises two different siRNAs targeting two different genes or pharmaceutically acceptable salts thereof, wherein the two different siRNAs or salts thereof are linked by a ligand for delivering nucleic acid and thereof integrated into a single entity, each of the siRNAs is a dsRNA composed of a sense strand and an antisense strand, and the two different genes are selected from any two of angiotensinogen (AGT), proprotein convertase subtilisin/kexin type 9 (PCSK9) and angiopoietin-like 3 (ANGPTL3);

• wherein the base composition of the siRNA targeting the AGT gene is selected from any one of the following dsRNA sequences, or a sequence having a sense strand or antisense strand that differs by no more than 1 nucleotide therefrom:
• A) 1167f:
• the sense strand thereof is shown in SEQ ID NO:
• 59, and the antisense strand thereof is shown in SEQ ID NO:
• 60;
• B) 1167b:
• the sense strand thereof is shown in SEQ ID NO:
• 51, and the antisense strand thereof is shown in SEQ ID NO:
• 52;
• C) 1165d:
• the sense strand thereof is shown in SEQ ID NO:
• 39, and the antisense strand thereof is shown in SEQ ID NO:
• 40;
• D) 1165f:
• the sense strand thereof is shown in SEQ ID NO:
• 43, and the antisense strand thereof is shown in SEQ ID NO:
• 44;
• wherein the base composition of the siRNA targeting the PCSK9 gene is selected from any one of the following dsRNA sequences, or a sequence having a sense strand or antisense strand that differs by no more than 1 nucleotide therefrom:
• E) 11040a:
• the sense strand thereof is shown in SEQ ID NO:
• 375, and the antisense strand thereof is shown in SEQ ID NO:
• 376;
• F) 11002d:
• the sense strand thereof is shown in SEQ ID NO:
• 259, and the antisense strand thereof is shown in SEQ ID NO:
• 260;
• G) 11002a:
• the sense strand thereof is shown in SEQ ID NO:
• 253, and the antisense strand thereof is shown in SEQ ID NO:
• 254;
• wherein the base composition of the siRNA targeting ANGPTL3 is selected from any one of the following dsRNA sequences, or a sequence having a sense strand or antisense strand that differs by no more than 1 nucleotide therefrom:
• H) 7061f:
• the sense strand thereof is shown in SEQ ID NO:
• 579, and the antisense strand thereof is shown in SEQ ID NO:
• 580;
• I) 7061b:
• the sense strand thereof is shown in SEQ ID NO:
• 571, and the antisense strand thereof is shown in SEQ ID NO:
• 572.