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A living cell's primary tasks of obtaining, transforming, and using energy to do work may seem simple. However, the second law of thermodynamics explains why these tasks are harder than they appear. None of the energy transfers in the universe are completely efficient. In every energy transfer, some amount of energy is lost in a form that is unusable. In most cases, this form is heat energy. Thermodynamically, heat energy is defined as the energy transferred from one system to another that...

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Related Experiment Video

Updated: Jun 21, 2025

DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation

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Published on: December 29, 2021

Spatially Localized Entropy-Driven Evolution of Nucleic Acid-Based Constitutional Dynamic Networks for Intracellular

Nina Lin¹, Yu Ouyang², Yunlong Qin²

¹School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.

Journal of the American Chemical Society

|July 16, 2024

Summary

We developed a DNA circuit that uses entropy to target cancer cells. This programmable system silences two genes, leading to cancer cell death and tumor reduction in mice.

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Area of Science:

Biochemistry
Molecular Biology
Nanotechnology

Background:

Constitutional dynamic networks (CDNs) offer programmable molecular assembly.
DNA nanotechnology provides a platform for developing targeted therapeutics.

Purpose of the Study:

To introduce a primer-guided, entropy-driven method for high-throughput evolution of DNA-based CDNs.
To develop a programmable, localized DNA circuit for cancer theranostics.

Main Methods:

Engineered a DNA tetrahedron circuit with tethers and siRNA cages.
Utilized miRNA-21 to trigger siRNA release and HIF-1α mRNA silencing.
Employed miRNA-155 to reconfigure the CDN for EGR-1 mRNA cleavage via a DNAzyme.

Main Results:

Achieved programmable, cooperative bis-gene silencing of HIF-1α and EGR-1.
Demonstrated enhanced cancer cell permeation via the DNA tetrahedron nanostructure.
Showcased effective apoptosis of breast cancer cells and tumor inhibition in mice.

Conclusions:

The entropy-driven CDN evolution provides a catalytic principle for amplified network emergence.
The localized DNA circuit enables effective in vitro and in vivo theranostics.
miRNA-triggered reconfiguration leads to programmable bis-gene silencing and selective cancer cell apoptosis.