Toehold-Mediated Shape Transition of Nucleic Acid Nanoparticles.

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Nucleic acid nanoparticles (NANPs) offer versatile platforms for molecular engineering.
• Controlled shape-switching in NANPs is crucial for developing advanced nanodevices.
• Isothermal conditions are desirable for practical applications of nanodevices.

Purpose of the Study:

• To develop a toehold-mediated strand displacement strategy for regulated shape-switching of NANPs.
• To enable sequential transformation of NANP architectures (e.g., triangular to hexagonal) under isothermal conditions.
• To integrate split fluorogenic aptamers for real-time monitoring of shape transitions.

Main Methods:

• Toehold-mediated strand displacement for NANP shape transformation.
• Electrophoretic mobility shift assays, atomic force microscopy, and dynamic light scattering for characterization.
• Incorporation of malachite green (MG), broccoli, and mango aptamers for real-time reporting.

Main Results:

• Demonstrated sequential shape transitions of NANPs from triangular to hexagonal architectures.
• Confirmed shape transitions using multiple biophysical characterization techniques.
• Showcased differential activation of MG, broccoli, and mango aptamers based on NANP geometry.
• Developed an RNA fluorogenic platform capable of logic gate operations (AND gate).
• Polygonal NANPs exhibited effective cellular internalization and gene silencing capabilities.

Conclusions:

• The toehold-mediated strand displacement strategy enables controlled, sequential shape-switching of NANPs.
• Integrated aptamer reporters allow for real-time monitoring of specific NANP transformations.
• The developed platform supports the creation of logic gates and demonstrates potential in biosensing and therapeutic applications.
• This work advances nucleic acid nanotechnology for designing sophisticated nanodevices.