Fig. 1: Engineering versatile synthetic receptors capable of sensing natural and engineered soluble ligands.
From: Engineered receptors for soluble cellular communication and disease sensing
a, Clinical and research applications for engineered receptors that are capable of soluble ligand detection. prgm, program; TF, transcription factor. b, Left, activation of a TGFβ-responsive SNIPR or synNotch driving a BFP reporter circuit in primary human CD3+ T cells after addition of recombinant human TGFβ1 (n = 2 technical replicates). Statistics calculated using two-way analysis of variance (ANOVA) with Å Ãdák’s multiple comparisons test; depicted significance corresponds to the comparison of SNIPR versus synNotch. Right, representative histograms of reporter expression level at the indicated concentrations of TGFβ. ****P < 0.0001. MFI, mean fluorescence intensity. c, Induction (left) and representative histograms (right) of a VEGF-sensing SNIPR→BFP circuit in primary human T cells through recombinant human VEGF (n = 3 technical replicates). The indicated significance corresponds to the comparison of SNIPR versus synNotch; two-way ANOVA with Å Ãdák’s multiple comparisons test. d, Receptor-mediated induction of a BFP reporter gene in primary human CD3+ T cells using recombinant human FGF2 (left) or IFNγ (right) (n = 2 technical replicates). e, Left, structural model of the de-novo-designed LHD heterodimer used to establish a bio-orthogonal receptor–ligand pair. Right, fold activation over background of an orthogonal ligand-responsive SNIPR or synNotch driving a BFP reporter circuit in Jurkat T cells through the introduction of orthoLigand C1-active (n = 3 technical replicates). Depicted significance corresponds to the comparison of SNIPR versus synNotch; two-way ANOVA with Å Ãdák’s multiple comparisons test.
