Researchers have designed artificial protein structures that mimic and build upon viral architecture, potentially opening new avenues for delivering therapeutic genes and vaccines. The breakthrough designs use artificial intelligence to create protein shells larger than previously possible, with sophisticated multi-component structures.
Published in Nature | Estimated reading time: 4 minutes
Professor Sangmin Lee from POSTECH’s Department of Chemical Engineering, collaborating with 2024 Nobel Chemistry Laureate Professor David Baker from the University of Washington, has developed protein “nanocages” that address a key challenge in therapeutic delivery. These structures can carry three times more genetic material than conventional gene delivery vectors like adeno-associated viruses (AAV).
“Advancements in AI have opened the door to a new era where we can design and assemble artificial proteins to meet humanity’s needs,” said Professor Lee. “We hope this research not only accelerates the development of gene therapies but also drives breakthroughs in next-generation vaccines and other biomedical innovations.”
The research team used AI-driven computational design to create protein structures in tetrahedral, octahedral, and icosahedral shapes. While viruses typically display symmetrical structures with subtle asymmetries, the team was able to recreate and expand upon these characteristics. The resulting nanostructures comprise four types of artificial proteins forming intricate architectures with six distinct protein-protein interfaces.
The largest structure, measuring 75 nanometers in diameter, represents a significant advancement over existing delivery systems. Electron microscopy confirmed that these AI-designed nanocages achieved precise symmetrical structures as intended. Functional experiments demonstrated their ability to effectively deliver therapeutic payloads to target cells.
The implications extend beyond gene therapy. These structures could potentially serve as platforms for vaccine development, with their multiple components allowing for sophisticated presentation of various immune-stimulating molecules. The ability to precisely control their assembly and modification opens possibilities for targeted drug delivery and other biomedical applications.
Glossary:
- Nanocage: An engineered protein structure that forms a cage-like shape at the nanoscale, capable of carrying therapeutic molecules
- Protein-protein interface: The region where two proteins connect and interact with each other
- Electron microscopy: A technique using electron beams instead of light to create highly detailed images of extremely small structures
Test Your Knowledge
What advantage do these new nanocages have over conventional delivery vectors?
They can carry three times more genetic material than conventional gene delivery vectors like adeno-associated viruses.
What three geometric shapes were the researchers able to create?
The team created protein structures in tetrahedral, octahedral, and icosahedral shapes.
How many distinct protein-protein interfaces do these new structures have?
The nanostructures have six distinct protein-protein interfaces formed by four types of artificial proteins.
What role did artificial intelligence play in this research?
AI was used for computational design to create protein structures that mimic and expand upon viral architecture, allowing for precise control of complex multi-component assemblies.
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