Virus that threatened humanity opens the future

Viruses are uniquely designed to encapsulate genetic material within a globular protein shell, 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 limits the amount of genetic material they can carry, and their simple design cannot replicate the versatility of native viral proteins.

To address these limitations, the research team used artificial intelligence-driven computational design. While most viruses display a symmetrical structure, they also possess subtle asymmetries. Using artificial intelligence, the team recreated these subtle features and successfully designed nanocages in tetrahedral, octahedral and icosahedral shapes for the first time.

The resulting nanostructures were composed of four types of artificial proteins, forming complex structures with six different protein-protein interfaces. Among them, the icosahedral structure with a diameter of up to 75 nanometers stands out because it can accommodate three times more genetic material than traditional gene delivery vectors such as adeno-associated virus (AAV), marking a major advancement in gene therapy.

Electron microscopy confirmed that the artificial intelligence-designed nanocage achieved the expected precise symmetrical structure. Functional experiments further demonstrated their ability to efficiently deliver therapeutic payloads to target cells, paving the way for practical medical applications.

“Advances in artificial intelligence have opened the door to a new era where we can design and assemble artificial proteins to meet human needs,” said Professor Lee Sang-min. “We hope this research will not only accelerate the development of gene therapies but also drive breakthroughs in next-generation vaccines and other biomedical innovations.”

Professor Li previously worked as a postdoctoral researcher in Professor Baker’s laboratory at the University of Washington for nearly three years from February 2021 to the end of 2023, and joined Pohang University of Science and Technology in January 2024.

This research was supported by the Korea Ministry of Science, Information and Communications’ Distinguished Young Scientist Program, Nano and Materials Technology Development Program, and Global Frontier Research Program, with additional funding provided by the Howard Hughes Medical Institute (HHMI) in the United States.