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.

Embodiments of the present invention generally relate to recombinant alpha 1-antitrypsin (AAT) proteins, including variants of human AAT with individually introduced mutations, compositions containing such recombinant AAT proteins and carriers, expression plasmids or vectors and host cells that express such recombinant AAT proteins, methods of producing such recombinant AAT proteins, and methods of treating AAT deficiency-related diseases, disorders, and conditions or diseases, disorders, and conditions resulting in protease-induced tissue damage in a subject in need thereof with the recombinant AAT proteins and/or recombinant AAT protein compositions described here. The recombinant AAT proteins derived from mammalian host cells as produced by the methods described here may be produced in large quantities, without any animal components, i.e., highly pure, highly glycosylated, and may be advantageously used over plasma-derived AAT.

The present invention provides a method of fractionating human plasma, in some embodiments, using the Cohn fractionation procedure. The improvement comprises the use of physiologically active reconstituted spray dried human plasma as the starting material for the fractionation procedure.

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 methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, A1ATD associated liver disease, and pulmonary disease, such as, A1ATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting A1AT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, A1ATD associated liver disease and pulmonary disease, such as, A1ATD associated pulmonary disease.

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.

This disclosure provides vectors and strategies for increasing the efficiency of gene therapy in hepatocytes. The efficiency of the delivery of a corrected gene or wild type gene is improved through the use of delivery to hepatocytes via intrahepatic (parenchyma) administration or administration via the portal vein. In addition, the corrected gene or wild type gene is delivered using an isolated exogenous nucleic acid comprising a promoter that is specifically expressed in hepatocytes. These methods and isolated exogenous nucleic acids are useful to correct gene defects in the liver such as inherited diseases of the liver.

This disclosure is directed to a fusion protein composition comprising an alpha-1-antitrypsin or α1-antitrypsin (also known as A1AT, A1A, or AAT) polypeptide (AAT), a modified AAT (mAAT) or a functional variant thereof and a bioactive polypeptide. This disclosure is particularly directed to a pharmaceutical composition comprising the fusion protein for treating a disease, such as a cancer or an autoimmune disease. The bioactive polypeptide can be a peptide hormone, interferon, or cytokine, such as interleukin-2 (IL-2), a modified IL-2 (mIL-2), IL-15, G-CSF, GM-CSF, IFN-α2, IFN-β1, GLP-1, FGF21, sdAb, a fragment thereof, a modified polypeptide thereof, or a combination thereof. One advantage of the fusion protein is to enhance the activity, stability, bioavailability or a combination thereof, of the bioactive polypeptide.

Alveolar-like macrophages and a method for generating alveolar-like macrophages from hemangioblasts is provided. The method comprises the steps of: i) culturing the hemangioblasts in a hematopoietic-inducing medium comprising vascular endothelial growth factor (VEGF), stem cell factor (SCF) and interleukin-3 (IL-3) for a sufficient period of time to generate macrophages, and ii) culturing the macrophages in an alveolar macrophage-inducing medium comprising granulocyte macrophage colony stimulating factor (GM-CSF), and optionally macrophage colony stimulating factor (M-CSF), under suitable conditions and for a sufficient period of time to yield alveolar-like macrophages.

We describe peptides and their uses for the treatment of autoimmune, inflammatory and metabolic diseases.