Abstract: Disclosed are systems and methods for detecting extracellular ligands. The disclosed systems and method for detecting extracellular ligands typically comprise or utilize engineered red blood cells (eRBCs) that comprises modular extracellular sensors. The eRBCs may comprise: (i) a first exogenous extracellular sensor; the first extracellular sensor comprising: a) a ligand binding domain, b) a transmembrane domain, and c) a first fragment of a functional protein, and (ii) a second exogenous extracellular sensor; the second extracellular sensor comprising: a) a ligand binding domain, b) a transmembrane domain, and c) a second fragment of the functional protein.

Abstract: Disclosed are systems and methods for detecting extracellular ligands. The disclosed systems and method for detecting extracellular ligands typically comprise or utilize engineered red blood cells (eRBCs) that comprises modular extracellular sensors. The eRBCs may comprise: (i) a first exogenous extracellular sensor; the first extracellular sensor comprising: a) a ligand binding domain, b) a transmembrane domain, and c) a first fragment of a functional protein, and (ii) a second exogenous extracellular sensor; the second extracellular sensor comprising: a) a ligand binding domain, b) a transmembrane domain, and c) a second fragment of the functional protein.

Abstract: 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.

Abstract: Disclosed are systems, components of systems, and methods for sensing extracellular ligands and/or modulating expression of an endogenous or exogenous gene in a cell. In some embodiments, the disclosed systems and methods comprise or utilize first and second exogenous extracellular sensors and/or nucleic acid sequences encoding the first and second exogenous extracellular sensors, wherein the first exogenous extracellular sensor comprises: a) a ligand binding domain; b) a transmembrane domain; c) a protease cleavage site; and d) a functional domain comprising an RNA-binding subdomain fused to a transcription regulatory subdomain; and the second exogenous extracellular sensor comprises: e) a ligand binding domain, f) a transmembrane domain, and g) a protease domain that cleaves the protease cleavage site of the first exogenous extracellular receptor.

Abstract: Disclosed are systems and methods for detecting extracellular ligands. The disclosed systems and method for detecting extracellular ligands typically comprise or utilize engineered red blood cells (eRBCs) that comprises modular extracellular sensors. The eRBCs may comprise: (i) a first exogenous extracellular sensor; the first extracellular sensor comprising: a) a ligand binding domain, b) a transmembrane domain, and c) a first fragment of a functional protein, and (ii) a second exogenous extracellular sensor; the second extracellular sensor comprising: a) a ligand binding domain, b) a transmembrane domain, and c) a second fragment of the functional protein.