AI-designed ‘nanocage’ mimics virus behavior to enhance gene therapy

Researchers have developed an innovative treatment platform by using artificial intelligence (AI) to mimic the complex structure of the virus. Their pioneering research was published in the journal Nature on December 18th.

Viruses are uniquely designed to encapsulate genetic material within a spherical protein shell, allowing the virus to replicate and invade host cells, often causing disease. Inspired by these complex structures, researchers have been studying artificial proteins modeled after viruses.

These “nanocages” mimic the behavior of viruses 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 falls short of replicating the multifunctionality of natural viral proteins.

To address these limitations, the research team used an AI-driven computing design. Although most viruses exhibit symmetric structures, they also feature subtle asymmetries. Using AI, the team was able to reproduce these subtle properties and design nanocages in tetrahedral, octahedral, and icosahedral shapes for the first time.

The resulting nanostructures are composed of four types of artificial proteins, forming a complex structure with six different protein–protein interfaces. Among them, icosahedral structures up to 75 nanometers in diameter stand out for their ability to hold three times more genetic material than traditional gene delivery vectors such as adeno-associated viruses (AAVs), making them useful for gene therapy. It brings about great progress. .

Electron microscopy confirmed that the AI-designed nanocage achieved the exact symmetric structure as intended. Functional experiments further demonstrated the ability to effectively deliver therapeutic payloads to target cells, paving the way for real-world medical applications.

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

For this research, Professor Lee collaborated with Professor David Baker of the University of Washington, winner of the 2024 Nobel Prize in Chemistry. Professor Lee previously worked as a postdoctoral researcher in Professor Baker’s laboratory for approximately three years from February 2021 to the end of 2023, and was assigned to POSTECH’s Chemical Engineering Department in January 2024.