This invention provides biosensors, cell models, and methods of their use for monitoring heme, oxygen or ATP. Biosensors can include targeting domains, sensing domains and reporting domains. Biosensors can be introduced into cells reprogrammed to represent experimental or pathologic cells of interest. Model cells expressing the biosensors can be contacted with putative bioactive agents to determine possible activities.

The present invention provides proteins comprising binding regions for cell-type specific targeting, Shiga toxin effector regions derived from A Subunits of members of the Shiga toxin family for providing Shiga toxin effector functions (e.g. cellular internalization and cytotoxicity), and carboxy-terminal endoplasmic reticulum localization signal motifs. The presently disclosed proteins can comprise additional exogenous materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, and are capable of targeted delivery of these additional exogenous materials into the interiors of target cells. The proteins of the present invention have uses in methods such as, e.g., methods involving targeted killing of target cells, delivering exogenous materials into target cells, labeling subcellular compartments of target cells, and diagnosing and/or treating a variety of conditions including cancers, tumors, other growth abnormalities, immune disorders, and microbial infections.

Compositions and methods are provided for modulating the activity of cells using engineered receptors, polynucleotide encoded engineered receptors, and gene therapy vectors comprising polynucleotides encoding engineered receptors. These compositions and methods find particular use in modulating the activity of neurons, for example in the treatment of disease or in the study of neuronal circuits.

The invention relates to protein-based T-cell receptor knockdown, and its use in T-cell therapies.

A genome-editing complex for modifying a target polynucleotide comprising a recombinant helical protein linked to either one or more molecules of a genome-editing system or a plasmid encoding for one or more molecules of a genome-editing system, wherein the helical protein length is in the range of from 5 nm to 25 nm, and width is in the range of from 1 nm to 5 nm.

The present disclosure relates to fusion proteins for inducing immune response and treating cancer, and particularly to fusion proteins for use as an immunogenic enhancer for inducing humoral immune response and cell-mediated immune response.

Provided are compositions and methods that block the interaction between Sonic hedgehog (Shh) and Surfeit locus protein 4 (SURF4), particularly for use in treating subjects with cancer or at risk of suffering from cancer. The subject methods block the interaction between SURF4 and Shh, either by mutating residue E50, D53, D56, or any combination thereof of SURF4 or mutating the CW motif (amino acid residues 32-38) on human Shh. Also provided is a composition comprising a polypeptide that contains the CW motif at the position of 32-38 on human Shh, a polypeptide that contains the first luminal loop (residues 49-60) of human SURF4, or small chemical molecules that block the interaction between SURF4 and Shh and administering said composition to a subject, particularly in subjects with cancer or at risk of suffering from cancer.

The present disclosure provides light-responsive polypeptides, and nucleic acids comprising nucleotide sequences encoding the light-responsive polypeptides. The present disclosure provides methods, devices, and systems for controlling the activity of a cell expressing a light-responsive polypeptide of the present disclosure.

The present invention provides compositions comprising a protein expression blocker or PEBL comprising a target-binding molecule and localizing domain, and methods of using such compositions in cancer therapy. PEBLs are useful as a blockade of expression of target surface receptors (peptides or antigens) in immune cells. Also provided herein are CD3/TCR-deficient T cells and CD3/TCR-deficient chimeric antigen receptor T cells that express such PEBLs.

A genome-editing complex for modifying a target polynucleotide comprising a recombinant helical protein linked to either one or more molecules of a genome-editing system or a plasmid encoding for one or more molecules of a genome-editing system, wherein the helical protein length is in the range of from 5 nm to 25 nm, and width is in the range of from 1 nm to 5 nm.