Engineering Whole Mammalian Cells for Target-Cell-Specific Invasion/Fusion

Area of Science:

• Synthetic biology
• Cellular engineering
• Molecular biology

Background:

• Mammalian cells possess complex mechanisms for intercellular interaction.
• Targeted manipulation of cell-cell interactions is crucial for therapeutic applications.
• Existing methods for cell targeting and delivery have limitations.

Purpose of the Study:

• To develop a synthetic system for targeted invasion and fusion of mammalian cells.
• To engineer invader cells capable of specific cell penetration and content release.
• To demonstrate the utility of this system for selective cell ablation.

Main Methods:

• Conjugation of RhoA activator to a transmembrane protein to induce localized RhoA activity upon cell contact.
• Expression of an acid-responsive fusogenic protein on invader cells.
• Utilizing target antigen expression on recipient cells for specific recognition.

Main Results:

• Synthetic induction of RhoA activity at the cell-cell interface mediated targeted cell invasion.
• Successful penetration of invader cells into recipient cells expressing a target antigen.
• Demonstrated invader/receiver cell fusion and subsequent release of intracellular contents into the recipient cytosol.
• Validated the system's efficacy for specific cell ablation.

Conclusions:

• The developed synthetic cell invasion and fusion system enables precise targeting and manipulation of mammalian cells.
• This technology offers a novel platform for cell-based cargo delivery.
• The system shows significant potential for targeted cell ablation therapies.