The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the Transmembrane protease, serine 6 (TMPRSS6) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a TMPRSS6 gene and to methods of preventing and treating a TMPRSS6-associated disorder, e.g., a disorder associated with iron overload and/or a disorder of ineffective erythropoiesis, e.g., hereditary hemochromatosis, β-thalassemia (e.g., β-thalassemia major and β-thalassemia intermiedia), polycythemia vera, myelodysplastic syndrome, congenital dyserythropoietic anemias, pyruvate kinase deficiency, erythropoietic porphyria, Parkinson's Disease, Alzheimer's Disease or Friedreich's Ataxia.

The present application pertains inter alia to an isolated vertebrate cell suitable for recombinant expression of a polypeptide of interest, wherein the vertebrate cell is altered to impair the function of the endogenous protease matriptase and wherein the cell comprises at least one heterologous polynucleotide encoding a polypeptide of interest and wherein the polypeptide of interest is secreted by the cell. It was found that using respective vertebrate cells for producing a recombinant polypeptide of interest significantly reduces clipping of the polypeptide of interest that is secreted into the cell culture medium. Also provided are improved production and screening methods.

A prodrugged antibody has a blocking moiety attached to a Cys on its heavy or light chain via a linker having a cleavable moiety. The blocking moiety inhibits binding of the antibody to its antigen. Cleavage of the cleavable moiety releases the blocking moiety and restores ability of the antibody to bind to its antigen.

The present invention provides mesenchymal stem cells (MSCs) and extracellular vesicles comprising exogenous membrane embedded proteins. Pharmaceutical compositions comprising MSCs and extracellular vesicles are also provided. The present invention further provides a method of treating, preventing or ameliorating a viral infection, inflammation, and/or tissue fibrosis.

The present application relates to protease substrates, peptide sequences cleavable by a protease, polypeptides comprising a protease cleavage sequence and methods for production thereof, pharmaceutical compositions comprising a polypeptide comprising a protease cleavage sequence, and methods for releasing an antigen-binding domain or a ligand by the cleavage of a protease cleavage sequence included in a polypeptide.

Provided are methods for and compounds for modulating the complement system. In particular, compounds are provided that inhibit complement activation and compounds are provided that promote complement activation. The compounds are therapeutics by virtue of their effects on the complement system. Hence, the compounds that inhibit complement activation can be used for treatment of ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, inflammatory diseases and diseases with an inflammatory component, including Alzheimer's Disease and other neurodegenerative disorders.

The present invention relates to nucleic acids for inhibiting expression of a target gene in a cell, comprising at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from said target gene to be inhibited. The first strand of the nucleic acid has a terminal 5′(E)-vinylphosphonate nucleotide that is linked to the second nucleotide in the first strand by a phosphodiester linkage.

Provided are MTSP-1 polypeptides modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to inhibit its activity and thereby inhibit complement activation. The modified MTSP-1 polypeptides that inhibit complement activation can be used for treatment of diseases and conditions in which complement activation plays a role. Such diseases and conditions include inflammatory diseases and diseases with an inflammatory component. Exemplary of these disorders are ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, ophthalmic disorders, such as diabetic retinopathies and macular degeneration, including age-related macular degeneration (AMD), and transplanted organ rejection, such as renal delayed graft function (DGF).

The present application pertains inter alia to an isolated vertebrate cell suitable for recombinant expression of a polypeptide of interest, wherein the vertebrate cell is altered to impair the function of the endogenous protease matriptase and wherein said cell comprises at least one heterologous polynucleotide encoding a polypeptide of interest and wherein the polypeptide of interest is secreted by the cell. It was found that using respective vertebrate cells for producing a recombinant polypeptide of interest significantly reduces clipping of the polypeptide of interest that is secreted into the cell culture medium. Also provided are improved production and screening methods.

A prodrugged antibody has a blocking moiety attached to a Cys on its heavy or light chain via a linker having a cleavable moiety. The blocking moiety inhibits binding of the antibody to its antigen. Cleavage of the cleavable moiety releases the blocking moiety and restores ability of the antibody to bind to its antigen.