Products, compositions, and their uses are provided. In particular, nucleic acid products that modulate, in particular interfere with or inhibit, Factor XI (FXI) gene expression are provided. The products can be oligomeric compounds that comprise at least a first region of linked nucleosides having at least a first nucleobase sequence that is at least partially complementary to at least a portion of RNA transcribed from an FXI gene, wherein said first nucleobase sequence is selected from the following sequences, or a portion thereof: SEQ ID NOs 1 to 250.

Compositions and methods are provided for treating, preventing, and/or alleviating at least one symptom of heart failure with preserved ejection fraction.

The present disclosure provides a GalNAc monomer comprising a ribose ring or a derivative structure thereof and a use thereof in liver-targeted delivery of small nucleic acid drugs. Specifically provided is a compound of formula (I) or a pharmaceutically acceptable salt thereof. The GalNAc-conjugated oligonucleotide prepared from the GalNAc compound provided by the present disclosure can achieve efficient liver-targeted delivery and enhance drug efficacy.

A high-activity blood coagulation factor XI mutant Ala570Thr (A570T), having nucleotide sequences as shown in SEQ ID NOs: 1-4 and an amino acid sequence as shown in SEQ ID NO: 5, is provided. The mutant is resistant to a physiological inhibitor thereof after being activated from a zymogen state to an active enzyme. Therefore, the mutant has a very high blood coagulation activity and a stronger catalytic ability for a non-physiological substrate; and the mutant is applied to the treatment of hemorrhagic diseases, and has good prospects in terms of gene therapy, gene editing and recombinant protein replacement treatments.