COMET

COMET provides programmable control of gene expression in mammalian cells by combining collections of activating and inhibitory zinc-finger transcription factors with cognate promoters to construct customizable genetic circuits.

Key Features:

• Extensive Component Library: COMET comprises 44 activating zinc-finger TFs, 12 inhibitory zinc-finger TFs, and 83 cognate promoters.
• Orthogonality and Characterization: Components are multiple orthogonal and well-characterized transcription factors that function independently without cross-interference.
• Scalability and Customizability: The framework accommodates addition of new parts to expand and customize genetic programs.
• Dynamic Range of Expression Control: The system can tune gene expression over three orders of magnitude.
• Chemically Inducible TF Activity: Transcription factor activity can be modulated in a chemically inducible manner.
• Boolean Logic Implementation: COMET supports single-layer Boolean logic operations within genetic circuits.
• Mechanistic Mathematical Model: The toolkit development includes a mathematical model that informs component interactions and system performance.

Scientific Applications:

• Synthetic Biology: Design and implementation of customizable genetic circuits in mammalian cells.
• Therapeutic Development: Engineering controllable gene expression systems for applications in cell-based and gene therapies.
• Gene Regulation Studies: Precise perturbation and measurement of gene regulatory mechanisms in mammalian systems.

Methodology:

The development included creation of a mathematical model that provides mechanistic insights into component interactions and system performance.