Adenosine-Triggered Dynamic and Transient Aptamer-Based Networks Integrated in Liposome Protocell Assemblies.

Area of Science:

• Biochemistry and Molecular Biology
• Synthetic Biology
• Nanotechnology

Background:

• Transient dissipative nucleic-acid-based reaction circuits and constitutional dynamic networks are emerging fields for emulating biological systems.
• Previous research utilized enzymes, DNAzymes, or light to control DNA networks, with integration into protocells being a key challenge.
• Developing versatile frameworks for dynamic DNA circuits and their application in protocell models is an active area of research.

Purpose of the Study:

• To introduce a versatile adenosine (AD)/adenosine deaminase (ADA) recognition/catalytic framework for driving transient DNAzyme circuits and dissipative constitutional dynamic networks.
• To integrate these AD/ADA-driven transient frameworks into liposome assemblies as protocell models.
• To demonstrate the potential of these engineered protocells in targeted cancer gene therapy.

Main Methods:

• Developed an allosterically AD-stabilized DNAzyme circuit and a dissipative AD-stabilized constitutional dynamic network using the AD/ADA system.
• Integrated the AD/ADA-driven transient frameworks into liposome assemblies to create protocell models.
• Functionalized liposomes with ATP-stabilized DNAzymes targeting EGR-1 mRNA and fused them with MCF-7 breast cancer cells.

Main Results:

• Successfully created transient, allosterically controlled DNAzyme circuits and dissipative constitutional dynamic networks driven by the AD/ADA framework.
• Demonstrated the integration of these dynamic DNA systems within liposome-based protocell models.
• Achieved selective apoptosis in MCF-7 breast cancer cells through functionalized liposomes delivering EGR-1 mRNA-cleaving DNAzymes.

Conclusions:

• The AD/ADA recognition/catalytic framework offers a versatile platform for constructing transient, allosterically controlled DNA-based circuits and networks.
• The integration of these dynamic DNA systems into protocell models provides a promising approach for developing advanced biological systems.
• This study showcases the potential of engineered protocells for targeted gene therapy, specifically inducing apoptosis in breast cancer cells via mRNA degradation.