Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

The present invention relates to a recombinant nucleic acid construct encoding a kallikrein-2 fusion protein. The kallikrein-2 fusion protein includes a first nucleotide sequence encoding kallikrein-2 (KLK2), and a second nucleotide sequence encoding a glycosylphophatidylinositol (GPI) attachment sequence, where the GPI attachment sequence encoding nucleotide sequence is positioned 3′ to the KLK2 encoding nucleotide sequence. Also disclosed are vectors, preparations of cells, and methods of use thereof

Short-acting Factor VII peptides are disclosed. A shortened half-life is desirable for treatment of acute bleeding and similar disorders. Modification of the sialylation and/or glycosylation of Factor VII and variants thereof produced peptides useful in treating conditions of acute bleeding.

The invention relates to synthetic liver-specific promoters and expression constructs for producing polypeptides and functional nucleic acids in the liver of a subject. The invention further relates to optimized polynucleotide sequences encoding Factor IX proteins, vector comprising the same, and methods of using these compositions to treat a bleeding disorder.

The present invention relates to a novel polypeptide which displays IgG cysteine protease activity, and in vivo and ex vivo uses thereof. Uses of the polypeptide include methods for the prevention or treatment of diseases and conditions mediated by IgG, and methods for the analysis of IgG.

Aspects of the disclosure relate to methods and compositions useful for in vivo and/or in vitro enzyme profiling. In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of signature molecules as representative of the presence of active enzymes associated with diseases or conditions. In some embodiments, the disclosure provides compositions and in vitro methods for localization of enzymatic activity in a tissue sample.

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.

Improved dermal filler formulation comprising a hyaluronic acid and a botulinum toxin.

Provided are methods of identifying, visualizing and purifying proteases from a complex biological sample.

Provided is a unit dose of recombinant adeno-associated virus (AAV) particles for expression of matrix metalloproteinase 3 (MMP-3). Further provided is a unit dose of recombinant MMP-3. Also provided are methods of use thereof, e.g., in transducing the corneal endothelium of a subject; reducing intraocular pressure in an eye of a subject; treating and/or preventing elevated intraocular pressure in a subject; and treating and/or preventing glaucoma in a subject. Subjects include primates.