The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease.

Disclosed are methods of eliminating at least on target cell in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of immune cells, wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell, wherein specifically binding of the one or more CLR(s) to the target activates the immune cell, and wherein the activated immune cell induces death of the target cell. Exemplary target cells include, but are not limited to, hematopoietic stem cells (HSCs).

Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

The present invention provides, for example, a set of two polypeptides exhibiting the nuclease activity with dependence on light or in the presence of a drug, in which an N-terminal side fragment and a C-terminal side fragment of a Cas9 protein are bound to each of two polypeptides which form a dimer with dependence on light or in the presence of a drug.

The present invention relates to means and methods for optimizing expression of a heterologous polypeptide of interest in Gram-positive host cells by co-expression with a foldase that is cognate to the heterologous polypeptide of interest.

The present disclosure provides novel co-stimulatory domains useful in genetically-modified cells to promote cell proliferation and/or promote cytokine secretion after antigen recognition. For example, disclosed herein are genetically-modified cells comprising a chimeric antigen receptor or an inducible regulatory construct incorporating the co-stimulatory domains disclosed herein. Also disclosed herein are plasmids and viral vectors comprising a nucleic acid sequence encoding the co-stimulatory domains, and methods of administering compositions comprising the novel co-stimulatory domains to subjects in order to reduce the symptoms, progression, or occurrence of disease, such as cancer.

Disclosed is a dTAG system comprising a small molecule degraders of FKBP12-tagged proteins via recruitment of Von Hippel-Lindau E3 ubiquitin ligase (VHL) E3 ubiquitin ligase and uses thereof.

Methods are provided for assessing a clinical response to a glucocorticoid receptor antagonist (GRA) in a human subject and for diagnosing Cushing's syndrome.

Engineered polypeptides or engineered microbial cells useful in synthesizing acyl amino acids are provided. In some embodiments, engineered polypeptides or engineered microbial cells are useful in synthesizing acyl amino acids with one or more hydroxyl and/or methyl groups at one or more positions of the fatty acid portion of the acyl amino acid (e.g., at ω-1, ω-2, and/or ω-3 positions of the fatty acid portion of the acyl amino acid). Also provided are methods of making acyl amino acids using engineered polypeptides and/or engineered microbial cells.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.