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Researchers developed a universal platform for designer receptors, enabling cell therapies to detect diverse molecules. This generalized extracellular molecule sensor (GEMS) platform shows promise for targeted therapies and diagnostics.

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Area of Science:

  • Synthetic biology
  • Immunology
  • Biotechnology

Background:

  • Cell-based therapies require precise molecular detection for tailored responses.
  • Existing designer receptors have limitations in sensing diverse medically relevant molecules.

Purpose of the Study:

  • To develop a universal receptor scaffold for antibody-specific molecular input.
  • To enable the activation of various intracellular signaling pathways (JAK/STAT, MAPK, PLCG, PI3K/Akt) for transgene expression.
  • To create a versatile platform for detecting a wide range of molecules, from small chemicals to proteins.

Main Methods:

  • Designed and implemented the generalized extracellular molecule sensor (GEMS) platform.
  • Engineered antibody fragments targeting a synthetic azo dye, nicotine, a peptide tag, and prostate-specific antigen (PSA).
  • Rewired intracellular signaling pathways to synthetic promoters for transgene expression.

Main Results:

  • Demonstrated robust signaling and transgene expression with high signal-to-noise ratios for four distinct GEMS devices.
  • Achieved sensitivity in the clinically relevant range for nicotine and PSA detection.
  • Successfully detected pathological PSA levels in prostate cancer patient serum using PSA-specific GEMS.

Conclusions:

  • The GEMS platform offers a universal approach to engineer designer receptors for cell-based therapies.
  • This technology expands the sensor space for detecting diverse medically relevant molecules.
  • GEMS shows potential for developing advanced diagnostics and targeted therapeutic strategies.