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A groundbreaking study led by Professor Sangmin Lee from POSTECH’s Department of Chemical Engineering, in collaboration with 2024 Nobel Chemistry Laureate Professor David Baker of the University of Washington, has opened a new chapter in therapeutic technology. Their innovative research, which mimics the intricate structures of viruses using artificial intelligence (AI), promises to revolutionize gene therapy, vaccine development, and other biomedical innovations. The findings were published in Nature on December 18, 2024.
Viruses, although often harmful, have evolved highly specialized structures to encapsulate genetic material and replicate within host cells. This ability has long intrigued scientists seeking to harness the power of viral designs for medical applications. By mimicking the viral protein shells, known as nanocages, researchers have been able to develop delivery systems for therapeutic genes. However, previous attempts have faced significant limitations due to the size constraints of these nanocages and their inability to replicate the multifunctional nature of natural viral proteins.
To overcome these challenges, the research team leveraged AI-driven computational design, a cutting-edge technology that allowed them to recreate not only the symmetrical but also the subtle asymmetries present in natural viral structures. The result was the creation of nanocages in tetrahedral, octahedral, and icosahedral shapes, marking a major leap in the field of artificial protein design.
The new nanostructures, composed of four types of artificial proteins, form complex architectures with six distinct protein-protein interfaces. Among these, the icosahedral nanocage, measuring up to 75 nanometers in diameter, stands out for its remarkable ability to carry three times more genetic material than current gene delivery systems like adeno-associated viruses (AAV). This advancement is expected to dramatically improve the efficiency and scope of gene therapies, offering a more powerful tool for treating genetic disorders.
Electron microscopy confirmed the precision of these AI-designed nanocages, validating the team’s ability to achieve the desired symmetrical structures. Functional experiments also demonstrated their effectiveness in delivering therapeutic payloads to target cells, bringing this innovative technology closer to real-world medical applications.
Professor Lee expressed his excitement over the potential impact of this work: “Advancements in AI have opened the door to a new era where we can design and assemble artificial proteins to meet humanity’s needs. We hope this research not only accelerates the development of gene therapies but also drives breakthroughs in next-generation vaccines and other biomedical innovations.”
Professor Lee’s collaboration with Professor Baker is built on a strong academic foundation, as Lee worked in Baker’s laboratory at the University of Washington from February 2021 to late 2023 before joining POSTECH in January 2024.
This transformative study was supported by several funding sources, including the Republic of Korea’s Ministry of Science and ICT under the Outstanding Young Scientist Program, the Nano and Material Technology Development Program, and the Global Frontier Research Program. Additional support came from the Howard Hughes Medical Institute (HHMI) in the United States.
The research heralds a new era in biotechnology, where AI and viral-inspired structures could lead to more effective treatments for a range of diseases, including genetic disorders and viral infections, and unlock novel approaches to vaccine and therapeutic development.
As humanity continues to battle pressing health challenges, this cutting-edge research demonstrates how the natural world, even in its viral forms, can hold the keys to our future medical advancements.
