A method for generating a reporter cell line comprises culturing a cell line capable of undergoing two or more consecutive stages of differentiation and performing the targeted insertion of two or more secretable reporter genes into the genome of the cultured cell line to form edited cells. One or more first stage inserted secretable reporter genes are placed under control of promoters for genes canonically expressed during the first stage of differentiation, and one or more second stage inserted secretable reporter genes are placed under control of promoters for genes canonically expressed during the second stage of differentiation but not during the first stage of differentiation. Differentiation of the clonally expanded edited cells is then induced to the first stage of differentiation, thus inducing expression of the first stage inserted secretable reporter genes.

Proteins, nucleic acids encoding the proteins, compositions comprising the proteins, and methods are provided. The proteins have the ability to be self-targeted to ICAM-1 and, if desired, enzymatically-released at acidic pH. The ICAM-1-targeting peptides are provided as single copies or multiples repeats, and can be separated by linkers from the enzyme segment, from which the ICAM-1 targeting peptides can be released, if desired, at acidic pH. These fusion proteins enhance the activity of the enzyme segment within or liberated from the fusion protein, and provide increased recognition and targeting of diseased organs, transport from the bloodstream across the endothelium into said diseased organ, and intracellular uptake and lysosomal trafficking by cells in them, both in peripheral tissues and the central nervous system. Representative nucleotide and amino acid sequences of these fusion proteins, as well as in vitro, cellular, and in vivo animal data are provided. The described proteins can be used as a protein therapy, a gene therapy, or an implanted cell therapy.

Materials and methods for using polypeptides containing fragments and variants of endostatin to treat fibrosis are described herein.

The present invention provides isolated plasmids, recombinant microorganisms, kits, and methods for the treatment of inflammatory skin disease.

The present disclosure provides genetically modified microorganisms (e.g., bacteria or yeast) with enhanced mucin-binding and/or cell-adhesion properties. For example, the present disclosure provides bacteria exhibiting increased in vitro binding to Caco-2 cells, and increased in vitro binding to mucins. Such microorganisms (e.g., bacteria) can be used, e.g., to deliver bioactive polypeptides to the gastrointestinal tract of a mammalian subject. Modifying the microorganism in the described manner allows for the modulation of gastrointestinal retention and transit times for the microorganism (e.g., bacterium). Exemplary microorganisms (e.g., lactic acid bacteria, such as Lactococcus lactis) contain an exogenous nucleic acid encoding a fusion protein containing a cell-adherence polypeptide, such as CmbA, and a mucin-binding polypeptide, such as a trefoil factor (TFF), e.g., human TFF3. The current disclosure further provides method for making and using the described microorganisms (e.g., bacteria).

The present invention relates to tumor necrosis factor (TNF) receptor superfamily (TNFRSF) receptor-activating antibody fusion proteins with FcyR-independent agonistic activity, and to compositions and methods related thereto.

Engineered bacteria that secrete therapeutic polypeptides, pharmaceutical compositions comprising the bacteria, methods for producing recombinant polypeptides, and methods for using the bacteria for diagnostic and therapeutic purposes are provided.

The present disclosure relates to methods for producing recombinant proteins, as well as compositions used in and produced by such methods. Specifically, the present disclosure relates to methods for producing high secreted yields of recombinant proteins, and the compositions provided herein include recombinant host cells that comprise polynucleotide sequences encoding proteins operably linked to at least 2 distinct secretion signals.

Described are methods, compositions, and devices for a concatemeric protein standard that behaves as a protein but transforms into single peptides upon digestion, which is optimized to function as a non-obtrusive process control for mass spectrometry analysis.

Novel programmable targeting sequences and applications thereof. The targeting sequences can be engineered for binding to proteins, polypeptides, and other macromolecules.