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OptoREACT: Optogenetic Receptor Activation on Nonengineered Human T Cells.

Anja Armbruster1,2,3, Anna K Ehret2,3,4,5, Marissa Russ2,3,4

  • 1INM - Leibniz Institute for New Materials, Campus D2 2, Saarbrücken 66123, Germany.

ACS Synthetic Biology
|February 9, 2024
PubMed
Summary

Researchers developed OptoREACT, a novel optogenetic system enabling light-controlled activation of cell surface receptors in non-genetically engineered cells. This breakthrough allows for precise manipulation of cellular signaling for therapeutic and research applications.

Keywords:
T cell receptorT cellsextracellular optogeneticsphytochromesprimary cellsreceptor activation

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Optogenetics offers powerful control over cellular processes but typically requires genetic modification.
  • This limitation restricts its use in primary cells, hindering physiological studies and therapeutic applications.

Purpose of the Study:

  • To develop a non-invasive, light-inducible system for activating cell surface receptors in non-engineered cells.
  • To overcome the limitations of genetic manipulation in optogenetic applications.

Main Methods:

  • Developed OptoREACT (Optogenetic Receptor Activation) using light-dependent interactions between phytochrome B (PhyB) and PIF6.
  • Utilized PIF6-coupled antibody fragments to target T cell receptors (TCRs) on Jurkat and primary human T cells.
  • Employed streptavidin-mediated tetramerization or cell surface immobilization of PhyB to induce receptor clustering and activation upon illumination.

Main Results:

  • Demonstrated successful light-dependent activation of TCRs in non-engineered T cells using the OptoREACT system.
  • Showcased the ability to cluster and activate cell surface receptors extracellularly without genetic manipulation.
  • Validated the system's potential by emulating T cell-antigen-presenting cell interactions.

Conclusions:

  • OptoREACT provides a versatile extracellular optogenetic approach for controlling cell surface receptors in primary, non-engineered cells.
  • This method expands the applicability of optogenetics in fundamental research and therapeutic development.
  • The system holds promise for light-controlled activation of diverse cell surface receptors.