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.

Fragile X syndrome (FXS) is the most common inherited form of human intellectual disability. FXS is caused by loss of function of the FMR1 gene which results in significant behavioral deficits in spatial learning and memory tests. FMR1−/− knockout mice share many of the learning deficits and decreased synaptic function encountered in FXS patients. Anecdotal evidence indicates a reduction in the amount of Reelin, a large extracellular signaling protein important for normal hippocampal synaptic plasticity, may play role in the etiology of FXS. Disclosed herein is a rAAV9 Reelin viral vector expressing a REELIN repeat R3+R6 fusion protein that is shown to rescue cognitive deficits in FMR1−/− mice as evaluated in the Hidden Platform Water Maze, Open Field and Fear Conditioning. Reelin gene therapy is therefore potentially a novel therapeutic for the treatment of Fragile X Syndrome.

The present invention relates to anti-MASP-2 inhibitory antibodies and compositions comprising such antibodies for use in inhibiting the adverse effects of MASP-2 dependent complement activation.

The present invention relates to the field of chromatography. More closely, the invention relates to a chromatographic method for purification of proteins, such as Factor VIII, von Willebrand factor and Factor IX. The chromatographic method is performed on a matrix comprising an inner porous core and outer porous lid surrounding said core.

The present disclosure is directed to peptide immunogen constructs targeting the catalytic domain of the PCSK9 protein, compositions containing the constructs, antibodies elicited by the constructs, and methods for making and using the constructs and compositions thereof. The disclosed peptide immunogen constructs have more than about 20 amino acids and contain (a) a B cell epitope having about more than about 7 contiguous amino acid residues from the PCSK9 and LDL-R receptor binding regions of the catalytic domain of the PCSK9 protein; (b) a heterologous Th epitope; and (c) an optional heterologous spacer. The disclosed PCSK9 peptide immunogen constructs stimulate the generation of highly specific antibodies directed to PCSK9 sites that are binding to LDL-R to allow for the prevention and/or treatment of patients with PCSK9 mediated disorders including an increased serum level of low-density lipoprotein cholesterol (LDL-C) and CV events.

The present disclosure relates to genetically modified non-human animals (e.g., genetically-modified mice or rodents) that express a hACE2 and/or hTMPRRS2 under control of the mouse promoter and the genetically modified non-human animal does not express native ACE2 and/or hTMPRRS2. The present disclosure also relates to methods of generating the genetically-modified animals (e.g., genetically modified mice or rodents), and methods of using the genetically modified non-human animals (e.g., genetically modified mice or rodents) described herein.

The present invention includes an antibody or antigen-binding fragment thereof that binds specifically to TMPRSS2 and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., influenza virus infections).

The invention relates to a novel inhibitor pharmacophore of PCSK9 and heteroaryl compounds that bind the PCSK9 protein.

Disclosed herein is one or more subtilisin variant, nucleic acid encoding same, and compositions and methods related to the production and use thereof, including one or more subtilisin variant that has improved stability and/or soil removal compared to one or more reference subtilisin.

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.