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Programmable Allosteric Regulation of Three-Dimensional DNA Nanostructures for Targeted Membrane Protein Degradation.
Zhen-Yao Wu1, Cuiyan Wu1, Ke Cai1
1Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education of China), Key Laboratory of Phytochemical R&D of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, P. R. China.
Nano Letters
|July 16, 2025
Summary
Researchers developed a programmable DNA nanostructure that precisely controls aptamer activity. This system enables targeted degradation of membrane proteins, offering a new method for molecular manipulation in research and disease management.
Area of Science:
- Biotechnology
- Molecular Biology
- Nanotechnology
Background:
- Precise regulation of membrane receptor activity is crucial for biological research and treating diseases.
- Existing methods for modulating membrane proteins have limitations in control and specificity.
Purpose of the Study:
- To design a programmable DNA nanostructure for precise, reversible, and functional modulation of aptamers.
- To achieve targeted degradation of membrane-associated proteins using DNA nanostructures.
- To explore the potential of allosteric regulation in DNA nanostructures for controlling molecular functions.
Main Methods:
- Rational design of a DNA nanostructure capable of housing and releasing aptamers.
- Utilizing fuel or anti-fuel strands to control aptamer positioning (interior/exterior) relative to the nanostructure.
- Demonstrating targeted degradation of membrane proteins triggered by aptamer exteriorization.
Main Results:
- The DNA nanostructure successfully prevented aptamer binding when the aptamer was internalized.
- Dynamic positioning of the aptamer using fuel/anti-fuel strands was achieved.
- Membrane protein degradation was observed exclusively when the aptamer was exposed externally.
Conclusions:
- Allosteric regulation within DNA nanostructures offers a novel approach for controlled membrane protein degradation.
- This programmable system provides a versatile platform for precise molecular manipulation.
- The findings open new avenues for therapeutic strategies and basic research involving membrane proteins.
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