The invention relates to a new, more potent, coagulation Factor IX (FIX) expression cassette for gene therapy of Haemophilia B (HB). Disclosed is a vector for expressing factor IX protein, the vector comprising a promoter, a nucleotide sequence encoding for a functional factor IX protein, and an intron sequence, wherein the intron sequence is positioned between exon 1 and exon 2 of the nucleotide sequence encoding for a functional factor IX protein, and wherein the intron sequence has at least 80% identity to the sequence of SEQ ID NO. 1 as disclosed herein.

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

The present invention provides a method for providing alpha-1 antitrypsin (?1-AT) to a subject, in particular a method for treating or preventing a disorder of disease associated with ?1-AT deficiency in the subject, wherein the method comprises providing, subcutaneously, a therapeutically or prophylactically effective amount of ?1-AT to the subject. Also provided is a composition and article of manufacture comprising ?1-AT, in particular a formulation suitable for subcutaneous administration of ?1-AT.

The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating alpha-1 antitrypsin deficiency (AATD) are described.

The invention relates to isolated nucleic acids and rAAV-based compositions, methods and kits useful for treating genetic diseases (e.g., alpha-1 antitrypsin deficiency).

Embodiments herein report compositions of and methods for making and using alpha-1 antitrypsin (AAT) fusion molecules or peptide derivatives thereof. In certain embodiments, compositions and methods relate to generating an AAT fusion molecule of use in pharmaceutically acceptable compositions to treat a subject in need of AAT therapy or treatment. In other embodiments, compositions and methods disclosed herein concern linking AAT or derivative thereof to an immune fragment.

A method of treating a bradykinin-mediated disease, wherein the method includes administering to a subject in need thereof an effective amount of a modified ?1 antitrypsin including a reactive center loop (RCL), wherein the residues P4-P1 of the RCL are selected from the group consisting of SMTR (SEQ ID NO: 12), SEAR (SEQ ID NO: 18), SMDR (SEQ ID NO: 23), SLGR (SEQ ID NO: 24), SKGR (SEQ ID NO: 25) and SMHR (SEQ ID NO: 27), wherein the modified al antitrypsin demonstrates increased inhibition of plasma kallikrein (PK) as compared to the corresponding unmodified ?1 antitrypsin, and wherein the modified ?1-antitrypsin more strongly inhibits PK than the modified ?1 antitrypsin inhibits either one of thrombin or APC.

This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a whey acidic protein (WAP) domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing such molecules.

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.