The present application discloses the use of light-gated cation-selective channelrhodopsins (Ch Rs) for the optogenetic control of the secretion of a polypeptide of interest in adipocytes. Engineered adipocytes comprising a channelrhodopsin (ChR) polypeptide, and/or a nucleic acid encoding same, and a secretory polypeptide precursor comprising a bioactive polypeptide and a signal peptide suitable for secretion of the bioactive polypeptide by the engineered adipocytes, and/or a nucleic acid encoding same, are disclosed. The use of such engineered adipocytes for the management or treatment of diseases/conditions in which the secretion of a polypeptide of interest is beneficial, such as the secretion of insulin in diabetic patients, is also disclosed.

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 recombinant Gram-negative bacterial strains and the use thereof for delivery of repeated domains of a heterologous protein or two or more domains of different heterologous proteins into eukaryotic cells.

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).

A recombinant fusion protein is disclosed. The fusion protein comprises: (a) a CD55 peptide sequence, (b) a linker sequence C-terminal to the CD55 sequence, (c) a transmembrane domain C-terminal to the linker sequence, and (d) an intracellular domain C-terminal to the transmembrane domain. The fusion protein does not contain a GPI anchor. The fusion protein can be expressed with an N-terminal secretory signal peptide, which is cleaved to yield the mature protein on the surface of a cell line or an enveloped virus. An oncolytic virus expressing the fusion protein is resistant to complement inactivation and can be used to treat cancer.

Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.

The present invention relates to a novel signal sequence peptide and a vector comprising a polynucleotide encoding same. The signal sequence peptide can induce a protein linked thereto to be secreted to the outside of a cell, and thus, when the signal sequence peptide is used or a recombinant microorganism transformed with the vector is used, the signal sequence peptide expresses a target protein and then secretes the target protein to the outside of a cell, thus enabling the target protein to exhibit the activity and function thereof.

Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.

Methods for producing heterologous multi-subunit proteins in transformed cells are disclosed. In particular, the present disclosure provides improved methods of producing multi-subunit proteins, including antibodies and other multi-subunit proteins, which may or may not be secreted, with a higher yield and decreased production of undesired side-products. In exemplary embodiments, the transformed cells are a yeast, e.g., methylotrophic yeast such as Pichia pastoris.

The disclosure provides nucleic acids, and variants and fragments thereof, obtained from strains of Bacillus thuringiensis encoding polypeptides having pesticidal activity against insect pests, including Lepidoptera. Particular embodiments of the disclosure provide isolated nucleic acids encoding pesticidal proteins, pesticidal compositions, DNA constructs, and transformed microorganisms and plants comprising a nucleic acid of the embodiments. These compositions find use in methods for controlling pests, especially plant pests.