Professor Sangmin Lee from POSTECH’s Department of Chemical Engineering, alongside Professor David Baker, the 2024 Nobel Laureate in Chemistry from the University of Washington, has created a groundbreaking therapeutic platform by replicating complex viral structures through artificial intelligence (AI). Their groundbreaking findings were shared in Nature on December 18.
Viruses are uniquely structured to encapsulate genetic material within spherical protein coats, which allows them to reproduce and penetrate host cells, often leading to illness. Inspired by these sophisticated forms, researchers have been experimenting with artificial proteins that imitate viruses. These “nanocages” act like viruses by delivering therapeutic genes effectively to specific cells. However, current nanocages encounter major limitations: their small size restricts the amount of genetic material they can transport, and their basic designs do not capture the multifunctional properties of natural viral proteins.
To overcome these challenges, the research team utilized computational design driven by AI. While most viruses are characterized by symmetrical features, they also possess subtle asymmetric traits. By harnessing AI, the team was able to replicate these delicate characteristics, successfully designing nanocages in shapes such as tetrahedrons, octahedrons, and icosahedrons for the first time.
The newly created nanostructures are made from four varieties of artificial proteins, which come together to form complex designs with six different protein-protein interaction sites. Notably, the icosahedral structure, which can reach diameters of up to 75 nanometers, is particularly remarkable for its capability to store three times the amount of genetic material compared to standard gene delivery methods, like adeno-associated viruses (AAV). This marks a notable progress in the field of gene therapy.
Electron microscopy validated that the AI-generated nanocages achieved the precise symmetrical forms that were intended. Functional tests further confirmed their efficacy in delivering therapeutic agents to targeted cells, setting the stage for real-world medical applications.
“The advancements in AI have ushered in a new era where we can design and construct artificial proteins tailored to human needs,” stated Professor Sangmin Lee. “We aspire that this research accelerates the advancement of gene therapies and also fosters breakthroughs in next-generation vaccines and other biomedical innovations.”
Professor Lee previously spent nearly three years as a postdoctoral researcher in Professor Baker’s lab at the University of Washington, from February 2021 until late 2023, before joining POSTECH in January 2024.
This research was supported by the Republic of Korea’s Ministry of Science and ICT through the Outstanding Young Scientist Program, the Nano and Material Technology Development Program, and the Global Frontier Research Program, with additional funding from the Howard Hughes Medical Institute (HHMI) in the United States.
