Combinations of an apyrase and an annexin, including fusion proteins thereof, are synergistic antithrombotics that do not induce unwanted bleeding

Curative and prophylactic therapies for microvascular and/or macrovascular thrombosis are provided, as are prophylactic therapies capable of preventing fibrinolysis shutdown and therapies for non-thrombotic disorders. Methods provide for administering a therapeutically effective amount of an annexin A2.

Compositions and methods are provided for loading cargoes onto red blood cells. Provided herein are novel antibodies, fragments, fusion proteins and other conjugates which specifically bind red blood cells via RHCE or Band 3.

Nucleic acid constructs and compositions that allow insertion of a FIX coding sequence into a target genomic locus such as an endogenous ALB locus and/or expression of the FIX coding sequence are provided. The nucleic acid constructs and compositions can be used in methods of introducing a F9 nucleic acid into a cell, methods of integration of a F9 nucleic acid into a target genomic locus, methods of expression of FIX in a cell, and in methods of treating hemophilia B or FIX deficiency in a subject.

The present invention concerns a recombinant microalgae comprising a nucleic acid sequence encoding a recombinant peptide of KTTKS (SEQ ID No 1); a recombinant peptide, polypeptide or protein consisting in repeated units of SEQ ID No 1; or a derivative thereof, said nucleic acid sequence being located in the chloroplast genome of microalgae. It also relates to a method for producing a recombinant peptide of SEQ ID No 1; a recombinant peptide, polypeptide or protein consisting in repeated units of SEQ ID No 1; or a derivative thereof, wherein said method comprises the chloroplast genome transformation of a microalgae with a nucleic acid sequence encoding said recombinant protein, polypeptide or peptide. It further relates to the use of said recombinant peptide, polypeptide or protein for the cosmetic industry.

The present invention concerns a recombinant microalgae comprising a nucleic acid sequence encoding a recombinant peptide of KTTKS (SEQ ID No 1); a recombinant peptide, polypeptide or protein consisting in repeated units of SEQ ID No 1; or a derivative thereof, said nucleic acid sequence being located in the chloroplast genome of microalgae. It also relates to a method for producing a recombinant peptide of SEQ ID No 1; a recombinant peptide, polypeptide or protein consisting in repeated units of SEQ ID No 1; or a derivative thereof, wherein said method comprises the chloroplast genome transformation of a microalgae with a nucleic acid sequence encoding said recombinant protein, polypeptide or peptide. It further relates to the use of said recombinant peptide, polypeptide or protein for the cosmetic industry.

The application describes ceDNA vectors having linear and continuous structure for delivery and expression of a transgene. ceDNA vectors comprise an expression cassette flanked by two ITR sequences, where the expression cassette encodes a transgene encoding FIX protein. Some ceDNA vectors further comprise cis-regulatory elements, including regulatory switches. Further provided herein are methods and cell lines for reliable gene expression of FIX protein in vitro, ex vivo and in vivo using the ceDNA vectors. Provided herein are method and compositions comprising ceDNA vectors useful for the expression of FIX protein in a cell, tissue or subject, and methods of treatment of diseases with said ceDNA vectors expressing FIX protein. Such FIX protein can be expressed for treating disease, e.g., hemophilia B.

The application describes ceDNA vectors having linear and continuous structure for delivery and expression of a transgene. ceDNA vectors comprise an expression cassette flanked by two ITR sequences, where the expression cassette encodes a transgene encoding FIX protein. Some ceDNA vectors further comprise cis-regulatory elements, including regulatory switches. Further provided herein are methods and cell lines for reliable gene expression of FIX protein in vitro, ex vivo and in vivo using the ceDNA vectors. Provided herein are method and compositions comprising ceDNA vectors useful for the expression of FIX protein in a cell, tissue or subject, and methods of treatment of diseases with said ceDNA vectors expressing FIX protein. Such FIX protein can be expressed for treating disease, e.g., hemophilia B.

The invention relates to isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D′D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders. The invention also relates to a method of extending or increasing half-life of a therapeutic polypeptide comprising a step of adding to the polypeptide sequence of said therapeutic polypeptide at least one sdAb directed against VWF D′D3 domain

The invention relates to isolated single-domain antibodies (sdAb) directed against von Willebrand Factor (VWF) D′D3 domain and chimeric polypeptides comprising thereof such as blood clotting factors and their uses in therapy such as in the prevention and treatment of hemostatic disorders. The invention also relates to a method of extending or increasing half-life of a therapeutic polypeptide comprising a step of adding to the polypeptide sequence of said therapeutic polypeptide at least one sdAb directed against VWF D′D3 domain