ATP-Powered Signaling Between Artificial and Living Cells

Area of Science:

• Biotechnology
• Synthetic Biology
• Molecular Engineering

Background:

• Adenosine triphosphate (ATP) is crucial for cellular energy and abundant in the tumor microenvironment.
• The tumor microenvironment's high ATP levels present a therapeutic target for cancer treatment.
• Existing cancer therapies can be limited by delivery mechanisms and specificity.

Purpose of the Study:

• To develop an artificial cell system for ATP-dissipative delivery of DNA signals to living cells.
• To engineer DNA signals for targeted intracellular uptake or extracellular instruction via cytokine-ssDNA chimeras.
• To investigate the system's design, integration, and regulation by ATP concentrations for therapeutic applications.

Main Methods:

• Designed an ATP-driven reaction network within artificial cells to transiently eject DNA signal strands.
• Developed customized DNA signals, including cytokine-ssDNA chimeras, for specific cellular interactions.
• Analyzed system components, timer circuits, and artificial cell architecture for efficient DNA delivery.
• Investigated the impact of varying ATP concentrations on the kinetics of DNA signal release.

Main Results:

• Successfully demonstrated ATP-dissipative delivery of DNA signals from artificial to living cells.
• Engineered signals capable of triggering intracellular downstream signaling programs upon uptake.
• Characterized the system's response to different ATP concentrations, enabling tunable DNA release.
• Validated the potential for selective delivery of therapeutic oligonucleotides in a cancer context.

Conclusions:

• The developed artificial cell system offers a novel platform for targeted DNA signal delivery.
• This strategy leverages the tumor microenvironment's ATP abundance for selective cancer therapy.
• The system shows promise for gene therapy, gene silencing, and advanced cancer treatment modalities.