The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

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.

Nucleic acid products are provided that modulate, interfere with or inhibit PCSK9 gene expression. The products include 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 a PCSK9 gene, wherein the first nucleobase sequence is selected from the following sequences, or a portion thereof: SEQ ID NOs 1 to 250 or 501 to 543.

The invention is directed to a composition comprising an (one or more) isolated peptide comprising a BF01 peptide, variants of a BF01 peptide and/or mutants of a BF01 peptide. In particular aspects, the composition is a pharmaceutical composition. The composition(s) can be used to inhibit thrombogenesis, selectively inhibit the intrinsic pathway of blood coagulation and selectively inhibit FX1 in an individual in need thereof comprising administering an effective amount of all or a biologically active portion of a BF01 peptide, one or more variants thereof and/or one or more mutants thereof.

Disclosed is a method for removing factor XI (FXI) during plasma protein purification, more specifically a method for removing FXI including dialyzing and concentrating a plasma protein fraction II paste containing FXI and a plasma protein, and then removing the FXI using a ceramic-based cation exchange resin. The method for removing factor XI (FXI) can improve removal efficiency of impurities and thrombogenic substances, thereby producing stable plasma proteins with improved quality.

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.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Various methods for evaluating hemostatic effect and various blood coagulation initiation reagents were studied to construct a method for evaluating blood coagulation reaction mediated by a substance having an activity of substituting for coagulation factor VIII (FVIII). As a result, it was discovered that by using a coagulation initiation reagent containing activated coagulation factor XI (FXIa) and phospholipids, the effect of a substance having an activity of substituting for coagulation factor VIII (FVIII) on blood coagulation reaction can be evaluated using the amount of thrombin generated in the blood sample as an indicator.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The invention relates to a method for preparing an irradiated platelet lysate, comprising the steps of providing a starting platelet lysate having platelet factors including growth factors and plasma proteins including coagulation factors and proteins other than the coagulation factors. Double irradiation of the starting platelet lysate, using UVC radiation and ionizing radiation. The double irradiation with UVC radiation and ionizing radiation being arranged to retain at least 75% of the total protein concentration of the starting platelet lysate, while reducing, by at least 40%, the concentration of at least one of the coagulation factors including fibrinogen, factor II, factor VII, factor IX, factor X and factor XI of the starting platelet lysate.