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Organ-Specific Gene Expression Control Using DNA Origami-Based Nanodevices
Yuxiang Liu1, Ruixuan Wang1, Qimingxing Chen1
1School of Life Science and Technology, ShanghaiTech University, Shanghai 201210 People's Republic of China.
Nano Letters
|June 26, 2024
Summary
Researchers developed robust DNA origami nanodevices encapsulated within lipid-based nanoparticles (LNPs) for enhanced organ-specific gene delivery. This breakthrough improves the functionality of messenger RNA (mRNA) and small interfering RNA (siRNA) in mouse organs.
Area of Science:
- Synthetic biology
- Nanotechnology
- Gene delivery
Background:
- Achieving organ-specific nanodevice function is a key goal in synthetic biology.
- DNA origami enables nanodevice construction for targeted delivery, but fragility and low targeting limit organ delivery.
- Current methods face challenges in maintaining nanostructure integrity under physiological conditions.
Purpose of the Study:
- To engineer robust DNA origami nanodevices for organ-specific gene delivery.
- To overcome the limitations of DNA nanostructure fragility and targeting.
- To enhance the functionality of gene of interest (GOI) payloads within target organs.
Main Methods:
- Construction of tough DNA origami nanostructures.
- Encapsulation of DNA origami into lipid-based nanoparticles (LNPs) under low pH conditions.
- Assessment of GOI (mRNA and siRNA) functionality in mouse organs.
- Cryogenic electron microscopy (Cryo-EM) for LNP structural analysis.
Main Results:
- Successfully created DNA origami-encapsulated LNPs stable under harsh conditions.
- Demonstrated increased functionality of mRNA and siRNA payloads within mouse organs.
- Identified distinct LNP structures contributing to enhanced payload delivery via Cryo-EM.
Conclusions:
- DNA origami-encapsulated LNPs offer a promising strategy for organ-specific gene delivery.
- The developed nanodevices enhance the efficacy of gene expression control.
- These findings provide a foundation for future advancements in targeted gene therapy and synthetic biology applications.
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