Engineering Multicellular Inter-Communication Systems Using a Synthetic Conformation Inducible Kinase Receptor

Area of Science:

• Synthetic biology
• Cellular engineering
• Biotechnology

Background:

• Synthetic multicellular systems are crucial for understanding cell interactions and developing cell-based therapies.
• Programming intercellular communication with spatiotemporal control remains a significant challenge.

Purpose of the Study:

• To introduce a novel synthetic receptor platform, synCIKER, for designing programmable multicellular inter-communication systems.
• To demonstrate synCIKER's ability to sense diverse inputs and control cellular behaviors.

Main Methods:

• Engineered tyrosine kinase receptors with input-responsive domains (chemical ligand, light, soluble protein).
• Rewired intracellular signaling pathways for controlled transgene expression.
• Utilized synCIKER to program receiver cell behaviors and construct logic gates.

Main Results:

• synCIKER successfully sensed inputs and generated customized secretory proteins to alter receiver cell functions, including receptor degradation and T cell-mediated lysis.
• Demonstrated the construction of cascade systems and intercellular Boolean logic gates (OR, AND, INHIBIT) for gene editing.
• Showcased synCIKER's capability to modulate macrophage polarization in multicellular systems.

Conclusions:

• The synCIKER platform offers a versatile tool for designing synthetic intercellular communication systems.
• This technology has significant potential for programming complex multicellular behaviors and advancing cell-based therapeutics.