Abstract: The present application relates to modular chimeric receptors, such as chimeric antigen receptors (CARs) comprising chimeric receptor and signaling modules with synthetic transmembrane domains that favor electrostatic interactions between the synthetic transmembrane domains in the cell membrane while eliminating or minimizing electrostatic interactions with the native transmembrane domains of immune receptors and signaling proteins. The modular chimeric receptors, which mimic the structure and signaling of native immune receptors, enable the distribution of the signaling domains across different cytoplasmic chains, display suitable surface expression as well as improved kinetics and sensitivities relative to current standard-of-care (SOC) CAR-based therapies.

Abstract: Described herein is a bioluminescence resonance energy transfer (BRET) based system and method to monitor ternary complex formation in real-time in live cells with high sensitivity and accuracy. This system transfers energy simultaneously between a luciferase donor and intermediate and terminal acceptors, appropriately chosen to also enable transfer from the intermediate to terminal acceptor while minimizing contaminating signals. The system may also be adapted for quaternary complex detection by including a protein complementation assay (PCA) component. The system is broadly applicable to the detection of any protein ternary/quaternary complex such as those involving nuclear receptors, GPCRs, Receptor Tyrosine Kinase (RTKs), multimeric enzymes or structural proteins.

Abstract: Described herein is a bioluminescence resonance energy transfer (BRET) based system and method to monitor ternary complex formation in real-time in live cells with high sensitivity and accuracy. This system transfers energy simultaneously between a luciferase donor and intermediate and terminal acceptors, appropriately chosen to also enable transfer from the intermediate to terminal acceptor while minimizing contaminating signals. The system may also be adapted for quaternary complex detection by including a protein complementation assay (PCA) component. The system is broadly applicable to the detection of any protein ternary/quaternary complex such as those involving nuclear receptors, GPCRs, Receptor Tyrosine Kinase (RTKs), multimeric enzymes or structural proteins.