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

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


Virus that threatened humanity opens the future
Cryo-EM evaluation of designed de novo protein nanocages. Credit score: POSTECH

Researchers have developed an modern therapeutic platform by mimicking the intricate constructions 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 duplicate and invade host cells, usually inflicting illness. Impressed by these advanced constructions, researchers have been exploring synthetic proteins modeled after viruses.

These “nanocages” mimic viral conduct, successfully delivering therapeutic genes to focus on cells. Nonetheless, current nanocages face vital challenges: their small measurement restricts the quantity of genetic materials they will carry, and their easy designs fall in need of replicating the multifunctionality of pure viral proteins.

To handle these limitations, the analysis staff used AI-driven computational design. Whereas most viruses show symmetrical constructions, additionally they function refined asymmetries. Leveraging AI, the staff 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 capacity to carry 3 times extra genetic materials than standard gene supply vectors, resembling adeno-associated viruses (AAV), marking a major development in gene remedy.

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

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

For this examine, 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 almost three years, from February 2021 to late 2023, earlier than becoming a member of POSTECH’s Division of Chemical Engineering in January 2024.

Extra info:
Sangmin Lee et al, 4-component protein nanocages designed by programmed symmetry breaking, Nature (2024). DOI: 10.1038/s41586-024-07814-1

Quotation:
AI-designed ‘nanocages’ mimic viral conduct for enhanced gene remedy (2024, December 24)
retrieved 26 December 2024
from https://phys.org/information/2024-12-ai-nanocages-mimic-viral-behavior.html

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