“Revolutionizing Gene Therapy: AI-Designed Nanocages Mimic Viral Structures for Enhanced Delivery”
Professor Sangmin Lee from POSTECH’s Department of Chemical Engineering, in collaboration with 2024 Nobel Chemistry Laureate Professor David Baker from the University of Washington, has made a groundbreaking advancement in the field of gene therapy by developing a novel therapeutic platform inspired by the intricate structures of viruses using artificial intelligence (AI). Their research, published in the prestigious journal Nature on December 18, has the potential to revolutionize the way gene therapies are delivered and pave the way for future biomedical innovations.
Viruses have evolved to encapsulate genetic material within protein shells, allowing them to replicate and infect host cells. Drawing inspiration from these complex structures, researchers have been exploring the use of artificial proteins known as “nanocages” to deliver therapeutic genes to specific cells. However, existing nanocages have faced limitations in terms of size and design complexity, hindering their effectiveness in gene delivery.
To overcome these challenges, Professor Lee and Professor Baker utilized AI-driven computational design to create nanocages with symmetrical and asymmetrical structures resembling those of natural viruses. By incorporating subtle asymmetries into the design, the research team was able to develop nanocages in tetrahedral, octahedral, and icosahedral shapes for the first time, enhancing their functionality and capacity for gene delivery.
The resulting nanostructures, composed of four types of artificial proteins, exhibited intricate architectures with multiple protein-protein interfaces, allowing them to carry significantly more genetic material than traditional gene delivery vectors like adeno-associated viruses (AAV). In particular, the icosahedral nanocage, measuring up to 75 nanometers in diameter, demonstrated the ability to hold three times more genetic material, marking a major breakthrough in gene therapy.
Electron microscopy analysis confirmed the precise symmetrical structures of the AI-designed nanocages, while functional experiments showcased their effectiveness in delivering therapeutic payloads to target cells. These findings have significant implications for the development of gene therapies and hold promise for future applications in vaccines and other biomedical innovations.
Professor Sangmin Lee expressed optimism about the potential impact of their research, stating, “Advancements in AI have enabled us to design and assemble artificial proteins to address critical medical needs. We believe that this work will not only accelerate the progress of gene therapies but also catalyze advancements in other areas of biomedicine.”
Prior to joining POSTECH, Professor Lee collaborated with Professor Baker at the University of Washington, where he worked as a postdoctoral researcher for nearly three years. The study was supported by funding from the Republic of Korea’s Ministry of Science and ICT, as well as the Howard Hughes Medical Institute in the United States, underscoring the global significance of this research endeavor.