Programmable single-cell mammalian biocomputers.

Area of Science:

• Synthetic biology
• Molecular biology
• Systems biology

Background:

• Synthetic biology advances enable programming cellular functions with standardized genetic devices.
• Designer networks mimic electronic circuits, executing genetic instructions with precision and robustness.
• Existing tools allow control over gene expression and translation.

Purpose of the Study:

• To design and implement synthetic transcription-translation control devices for plug-and-play rewiring.
• To demonstrate digital computations (NOT, AND, NAND, N-IMPLY) in single mammalian cells.
• To achieve programmable molecular arithmetic (half-subtractor, half-adder) using interconnected logic gates.

Main Methods:

• Utilized trigger-controlled transcription factors for gene expression control.
• Employed RNA-binding proteins to inhibit translation of specific RNA motifs.
• Designed combinatorial circuits integrating two-molecule inputs for logic operations.
• Interconnected synthetic logic gates to perform complex computations.

Main Results:

• Demonstrated NOT, AND, NAND, and N-IMPLY logic operations in single mammalian cells.
• Achieved bitwise intracellular XOR operations by functionally interconnecting two N-IMPLY variants.
• Successfully performed programmable half-subtractor and half-adder calculations using three logic gates.

Conclusions:

• Mammalian cells can execute basic molecular arithmetic functions with predictable, precise, and robust control.
• These engineered cells offer potential for new gene-based and cell-based therapies.
• Developed bio-electronic interfaces for future therapeutic applications.