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 invention relates to variants of acid-alpha glucosidase and uses thereof. Said variants are sequence-optimized and/or are linked to a heterogenous signal peptide.

Provided are an oncolytic virus and an application thereof, and a drug for treating a cancer. A first regulatory element and a second regulatory element are inserted into the genome of the oncolytic virus. The first regulatory element comprises a tumor-specific promoter and a first nucleic acid sequence, which is driven by the cancer cell specific promoter to express a specific protease in tumor cells; the second regulatory element comprises a second nucleic acid sequence for encoding an extracellular secretion signal peptide and a third nucleic acid sequence for encoding a specific cleavage site. The oncolytic virus can be replicated in tumor cells effectively to kill tumor cells while being safe to non-cancer cells.

Disclosed are methods and compositions related to polypeptides comprising a fusion of the needle tip protein and translocator protein of a type III secretion apparatus (T3SA) from a type III secretion system (T3SS) of a Gram negative bacteria. Disclosed herein are fusion polypeptides comprising a fusion of a needle tip protein, such as, Bsp22, LcrV, BipD, PcrV, CT053, or CT668, or anantigenic fragment thereof; and a translocator protein, such as, BopB, YopB, BipB, PopB, CopB, or CopB2, or anantigenic fragment thereof from a Type III secretion system (T3SS) of a Gram negative bacteria, such as, Bordetella, Burkholderia, Chlamydia, Pseudomonas, Vibrio, or Yersinia.

This invention relates to methods and compositions for binding antibodies. The methods may be used to isolate antibodies, treat disorders related to excess antibodies, acutely block antibodies to stop an autoimmune or inflammatory response, and inhibit neutralizing antibodies. In embodiments, the invention relates to methods of inhibiting neutralizing antibodies against a heterologous agent when the heterologous agent is administered to a subject, comprising administering to the subject an effective amount of Mycoplasma protein M or a functional fragment or derivative thereof, thereby inhibiting neutralization of the heterologous agent. The invention further relates to modified Mycoplasma protein M or functional fragments thereof having increased thermostability relative to wild-type protein M and their use in the methods of the invention.

The present invention relates to a method for preparing a fusion protein having an IgG Fc domain and, specifically, to a method for preparing a fusion protein having an IgG Fc domain, the method additionally comprising a step of culturing cells, which produce the fusion protein, at a decreased culture temperature, thereby increasing cell growth and cell viability so as to increase fusion protein productivity and inhibiting aggregate generation so as to improve quality and production yield.

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).

An endotoxin-free production of recombinant subunit vaccine components, and production methods thereof, using a synthetic virus-like-particle (VLP) to which is attached (and displayed) a fragment of the coronavirus “spike” protein, the Receptor Binding Domain (RBD) and wherein the VLP is produced very effectively using engineered B. subtilis.

The invention relates to methods of producing eukaryotic cell libraries encoding a repertoire of binding molecules (“binders”), wherein the methods use a site-specific nuclease for targeted cleavage of cellular DNA to enhance site-specific integration of binder genes through endogenous cellular repair mechanisms. Populations of eukaryotic cells are produced in which a repertoire of genes encoding binders are integrated into a desired locus in cellular DNA (e.g., a genomic locus) allowing expression of the encoded binding molecule, thereby creating a population of cells expressing different binders.

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.