AI Unlocks Virus Assembly Principles: Development of 'Protein Nanocages' for Vaccine Delivery [Reading Science]

Joint Research by Professor Sangmin Lee of POSTECH and Professor David Baker of the University of Washington

Published in Nature

"Potential for Drug and Gene Delivery Applications"

A team of Korean researchers has successfully designed large protein structures by utilizing artificial intelligence (AI) to replicate the assembly principles of natural viruses. This breakthrough is expected to serve as a next-generation delivery platform for vaccines, gene therapies, and targeted drugs.

On May 21, the Ministry of Science and ICT announced that Professor Sangmin Lee's research team from the Department of Chemical Engineering at Pohang University of Science and Technology, in collaboration with Professor David Baker's team at the University of Washington in the United States, has developed principles for designing artificial protein structures that self-assemble into virus-like forms. Professor David Baker was awarded the 2024 Nobel Prize in Chemistry.

Comparison of the natural virus capsid structure (left) and the protein nanocage designed by AI imitation (right). This image shows the application of the self-assembly principle of proteins forming spherical structures in viruses to the design of artificial proteins. Courtesy of the research team

This research was conducted with support from the Ministry of Science and ICT's Individual Basic Research Program (Outstanding Young Researcher) and the Nano and Material Technology Development Program, and was published in Nature, the world's most prestigious scientific journal.

The structure developed by the research team is called a "Protein Nanocage." These are hollow nanometer-scale structures formed by the self-assembly of multiple proteins, capable of encapsulating drugs, genetic material, or enzymes, and are gaining attention as next-generation drug delivery systems.

Existing artificial protein structure design technologies have mainly relied on perfect symmetry, which limited the scalability in size and shape. In contrast, natural viruses create large capsid structures by using the same protein hundreds or thousands of times, leveraging subtle differences in angles—a principle known as "quasisymmetry."

'AI Protein Shells' Assembled Like Viruses

The researchers focused on the fact that by precisely controlling the angles and curvature between protein blocks, a single protein can simultaneously form both pentagonal and hexagonal environments. Using this approach, they constructed a large domed, virus-like shell rather than a flat structure.

In particular, they used the AI-based protein structure generation tool "RFdiffusion" to design new connection structures. By setting a trimer as the basic building block and engineering them to interlock at different angles, they induced the formation of large structures from a single artificial protein.

The research team produced the designed proteins in Escherichia coli and examined their structures using cryo-electron microscopy. As a result, they observed the formation of various spherical structures ranging from at least 70 nm to up to 220 nm in size. The smallest structure resembled a "nano soccer ball," while the largest was more than three times its size.

Research team photo. (Left) Professor David Baker of the University of Washington (2024 Nobel Prize in Chemistry, corresponding author) and Professor Sangmin Lee of Pohang University of Science and Technology (first author & corresponding author). The photo was taken during Professor Lee's visit to the University of Washington in September 2025. Provided by the Ministry of Science and ICT.

This study is considered highly significant as it demonstrates the creation of virus-like structures solely using a single, newly AI-designed artificial protein, without recycling natural viral proteins.

The researchers plan to conduct follow-up studies to load drugs or genetic materials inside the structures. They also aim to develop technologies to control the size of these structures more uniformly by utilizing internal support proteins or nucleic acids.

Professor Sangmin Lee of Pohang University of Science and Technology explained, "Viruses are a representative example in nature showing that perfect symmetry is not the only way to build precise molecular structures. Our research demonstrates that even subtle adjustments in the angles between protein blocks can precisely control the final size and shape of the structure."

Kim Seongsu, policy chief at the Ministry of Science and ICT, stated, "This achievement proves that a Korean researcher, through collaboration with a Nobel laureate, has demonstrated world-class basic research capabilities. We will continue to actively support the production of world-leading research outcomes in the future."

This content was produced with the assistance of AI translation services.