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. Author manuscript; available in PMC: 2023 Apr 14.
Published in final edited form as: Cell. 2022 Apr 14;185(8):1431–1443.e16. doi: 10.1016/j.cell.2022.03.023

Figure 4. Enhanced sensitivity and tunable gene regulation through SNIPR engineering.

Figure 4.

(A) From analyzing activity of high-performing SNIPR-BFP circuits, the Notch1 TMD was selected for further testing. Three JMDs and two TMD alanine mutants were selected to produce a wide output range. (B) K562 cells transduced with a doxycycline-inducible FLAG-tagged ALPPL2 cassette express ALPPL2 in a dose-dependent manner. (C) CD4+ T cells expressing anti-ALPPL2 SNIPR-MCAM CAR circuits were co-incubated with sender cells for 48 hours and CAR output was measured using a t2a GFP system. (D) Graphical representation of C. (E) Supernatant IL-2 concentration was assayed using ELISA. (F) T cells stained with Cell Trace Violet were co-incubated with irradiated sender cells in media without IL-2 for 9 days. T cell proliferation was measured using flow cytometry.