AI-designed ‘nanocages’ mimic viral conduct for enhanced gene remedy

Researchers have developed an revolutionary therapeutic platform by mimicking the intricate buildings of viruses utilizing synthetic intelligence (AI). Their pioneering analysis was revealed in Nature on December 18.

Viruses are uniquely designed to encapsulate genetic materials inside spherical protein shells, enabling them to copy and invade host cells, usually inflicting illness. Impressed by these advanced buildings, researchers have been exploring synthetic proteins modeled after viruses.

These “nanocages” mimic viral conduct, successfully delivering therapeutic genes to focus on cells. Nevertheless, current nanocages face important challenges: their small dimension restricts the quantity of genetic materials they’ll carry, and their easy designs fall wanting replicating the multifunctionality of pure viral proteins.

To handle these limitations, the analysis group used AI-driven computational design. Whereas most viruses show symmetrical buildings, additionally they function delicate asymmetries. Leveraging AI, the group recreated these nuanced traits and efficiently designed nanocages in tetrahedral, octahedral, and icosahedral shapes for the primary time.

The ensuing nanostructures are composed of 4 kinds of synthetic proteins, forming intricate architectures with six distinct protein-protein interfaces. Amongst these, the icosahedral construction, measuring as much as 75 nanometers in diameter, stands out for its skill to carry thrice extra genetic materials than typical gene supply vectors, corresponding to adeno-associated viruses (AAV), marking a big development in gene remedy.

Electron microscopy confirmed the AI-designed nanocages achieved exact symmetrical buildings as meant. Practical experiments additional demonstrated their skill to successfully ship therapeutic payloads to focus on cells, paving the best way for sensible medical purposes.

“Developments in AI have opened the door to a brand new period the place we will design and assemble synthetic proteins to satisfy humanity’s wants,” mentioned Professor Sangmin Lee. “We hope this analysis not solely accelerates the event of gene therapies but additionally drives breakthroughs in next-generation vaccines and different biomedical improvements.”

For this research, Professor Lee collaborated with 2024 Nobel Chemistry Laureate Professor David Baker from the College of Washington. Professor Lee beforehand labored as a postdoctoral researcher in Professor Baker’s laboratory for practically three years, from February 2021 to late 2023, earlier than becoming a member of POSTECH’s Division of Chemical Engineering in January 2024.