Professor Sangmin Lee from the Department of Chemical Engineering at POSTECH, in collaboration with Professor David Baker, 2024 Nobel Laureate in Chemistry, from the University of Washington, has developed an innovative therapeutic platform by mimicking the intricate structures of viruses using artificial intelligence ( AI). His pioneering research was published in Nature on December 18.
Viruses are uniquely designed to encapsulate genetic material within spherical protein shells, allowing them to replicate and invade host cells, often causing disease. Inspired by these complex structures, researchers have been exploring artificial proteins modeled after viruses. These “nanocages” mimic viral behavior and effectively deliver therapeutic genes to target cells. However, existing nanocages face significant challenges: their small size restricts the amount of genetic material they can carry, and their simple designs fail to replicate the multifunctionality of natural viral proteins.
To address these limitations, the research team used an AI-powered computational design. While most viruses display symmetrical structures, they also exhibit subtle asymmetries. Leveraging AI, the team recreated these nuanced features and successfully designed nanocages in tetrahedral, octahedral, and icosahedral shapes for the first time.
The resulting nanostructures are composed of four types of artificial proteins, forming intricate architectures with six distinct protein-protein interfaces. Among them, the icosahedral structure, which measures up to 75 nanometers in diameter, stands out for its capacity to contain three times more genetic material than conventional gene delivery vectors, such as adeno-associated viruses (AAV), which represents a significant advance in gene therapy. .
Electron microscopy confirmed that the AI-designed nanocages achieved precise symmetrical structures as intended. Functional experiments further demonstrated its ability to effectively deliver therapeutic payloads to target cells, paving the way for practical medical applications.
“Advances in AI have opened the door to a new era in which we can design and assemble artificial proteins to meet the needs of humanity,” said Professor Sangmin Lee. “We hope this research will not only accelerate the development of gene therapies but also drive advances in next-generation vaccines and other biomedical innovations.”
Professor Lee previously worked as a postdoctoral researcher in Professor Baker’s laboratory at the University of Washington for almost three years, from February 2021 to the end of 2023, before joining POSTECH in January 2024.
This study was supported by the Ministry of Science and ICT of the Republic of Korea under the Outstanding Young Scientists Program, the Nano Technology and Materials Development Program and the Global Frontier Research Program, with additional funding provided by the Howard Hughes Medical Institute (HHMI) in the United States.