Published in the leading journal Nature on December 18, this groundbreaking research offers new hope for advanced gene delivery methods, next-generation vaccines, and other biomedical innovations.
Professor Sangmin Lee from the Department of Chemical Engineering at POSTECH, in collaboration with 2024 Nobel Chemistry Laureate Professor David Baker at the University of Washington, has pioneered an innovative therapeutic platform by recreating the intricate protein shells of viruses using artificial intelligence (AI). Their trailblazing findings, published on December 18 in Nature, promise to transform the field of gene therapy.
Reimagining Viruses for Medical Breakthroughs
Viruses are renowned for their highly evolved ability to enclose genetic material within spherical protein shells. These shells allow viruses to infect host cells and replicate, often leading to disease. Yet researchers have long been intrigued by this natural efficiency, exploring ways to develop artificial proteins that mimic viral structures. These so-called “nanocages” can deliver therapeutic genes directly into target cells. However, existing nanocage technologies have faced two major obstacles:
Limited Capacity – Their small size restricts the amount of genetic material they can carry.
Simple Design – Conventional nanocages lack the complex, multifunctional protein interfaces found in natural viruses.
AI-Driven Design: Beyond Symmetry
To overcome these challenges, Professor Lee’s team leveraged cutting-edge AI-driven computational design. While most known viruses exhibit symmetrical shapes, they also contain subtle asymmetries crucial for their function. Using AI, the researchers captured these nuanced features to create nanocages in tetrahedral, octahedral, and icosahedral forms—marking the first time such precise geometric variations have been achieved with synthetic proteins.
Revolutionary Nanocage Architectures
These newly designed nanostructures comprise four types of artificial proteins, resulting in complex architectures with six distinct protein-protein interfaces. Among the three configurations, the icosahedral nanocage—measuring up to 75 nanometers in diameter—stood out for its ability to encapsulate three times more genetic material than the widely used adeno-associated virus (AAV) vectors. This remarkable capacity represents a significant leap in improving gene therapy efficacy and opens doors to treating a broader range of genetic disorders.
Verification and Practical Impact
Advanced electron microscopy confirmed that the AI-designed nanocages assembled into precisely symmetrical structures as intended. Functional trials further validated their capacity to deliver therapeutic payloads into target cells, underscoring their potential clinical applications.
“Advancements in AI have opened the door to a new era where we can design and assemble artificial proteins to meet humanity's needs,” said Professor Sangmin Lee. “We hope this research not only accelerates the development of gene therapies but also propels breakthroughs in next-generation vaccines and other biomedical fields.”
Global Collaboration and Support
Prior to joining POSTECH in January 2024, Professor Lee served as a postdoctoral researcher in Professor Baker’s lab at the University of Washington from February 2021 to late 2023. Their joint research was made possible with funding from the Republic of Korea’s Ministry of Science and ICT—through programs such as the Outstanding Young Scientist Program, the Nano and Material Technology Development Program, and the Global Frontier Research Program—as well as additional support from the Howard Hughes Medical Institute (HHMI) in the United States.
With the ever-growing convergence of AI, synthetic biology, and molecular engineering, these virus-inspired nanocages represent a new frontier in healthcare innovation. By enabling the precise delivery of larger genetic payloads, researchers are poised to tackle rare genetic diseases, develop more effective vaccines, and potentially revolutionize cancer therapy. As AI continues to enhance the design and optimization of synthetic proteins, the future of medicine looks more promising than ever.