The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

Disclosed are systems and methods for detecting extracellular ligands and/or inducing expression of an exogenous or endogenous gene. The disclosed systems and methods typically include and/or utilize (i) first and second exogenous extracellular sensors, and third and fourth exogenous extracellular sensors; and (ii) an expression vector comprising a target gene operably linked to a hybrid promoter sequence. The hybrid promoter sequence of the expression vector includes a minimal promoter for inducing transcription and the hybrid promoter sequence further includes interspaced transcription regulator binding sites upstream of the minimal promoter that bind two or more transcription regulators of the extracellular sensors that are released from the extracellular sensors when the extracellular sensor bind an extracellular ligand.

Described herein is a method for editing the MHY7 gene in a cell by genome editing comprising introducing into the cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more double stranded breaks (DSBs) within or near enhancer regions of the MYH7 gene or MYH6 gene that results in deletion of one or more enhancer regions of the MYH7 gene.

Provided herein are mutants of estrogen receptor alpha ligand binding domain (ER-LBD), and inducible cell death systems that include mutants of estrogen receptor alpha ligand binding domain (ER-LBD). Also provided are methods of for use of the same, such as inducing cell death in a cell.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.

The technology described herein is directed to regulated synthetic gene expression systems. In one aspect described herein are synthetic transcription factors (synTFs) comprising a DNA binding domain, a transcriptional effector domain, and a regulator protein. In other aspects described herein are gene expression systems comprising said synTFs and methods of treating diseases and disorders using said synTFs.

Provided are molecular feedback circuits employing caged-degrons. Aspects of such circuits include the use of a caged-degron to modulate the output of a signaling pathway in a feedback-controlled manner. Also provided are nucleic acids encoding molecular circuits and cells containing such nucleic acids. Methods of using caged-degron-based molecular feedback circuits are also provided, including e.g., methods of modulating a signaling pathway of a cell that include genetically modifying the cell with a caged-degron-based molecular feedback circuit.

Provided herein are targeting constructs for sustained transgene expression of inducible cell death systems that include mutants of estrogen receptor alpha ligand binding domain (ER-LBD). Also provided are methods for use of the same, such as inducing cell death in a cell.

The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, which form into micro-clusters upon contacting a target or non-target cell.