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Engineering Versatile Two-Dimensional Nanobody-Origami Architectures for Enhanced Antiviral Activity
Tingjie Song1,2,3, Jazmin Galván Achi4, Varada Anirudhan4
1Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biorxiv : the Preprint Server for Biology
|July 9, 2025
Summary
Researchers developed a versatile DNA origami platform for creating antiviral nanobodies. This programmable system precisely arranges nanobodies to neutralize viruses like coronaviruses and retroviruses, significantly boosting therapeutic potential.
Area of Science:
- Nanotechnology
- Virology
- Biochemistry
Background:
- Pathogenic viruses pose a significant global health burden.
- Developing broad-spectrum antiviral therapies against families like coronaviruses and retroviruses is challenging.
Purpose of the Study:
- To engineer a programmable DNA origami platform for precise spatial arrangement of nanobodies.
- To create a versatile nano-architecture for broad-spectrum antiviral applications.
Main Methods:
- Utilized two-dimensional (2D) DNA origami for nanoscale spatial control.
- Site-selectively conjugated nanobodies (Nbs) to DNA oligonucleotides.
- Synthesized hybrid nano-architectures with tunable Nb patterns matching viral surface proteins.
Main Results:
- Achieved significant enhancement in viral binding affinity and neutralization potency.
- For SARS-CoV-2, a triangular Nb pattern showed a 171-fold improvement over monomeric Nbs (IC50 of 1.52 nM).
- For HIV, a 2D Nb nano-architecture increased neutralization efficiency by 233-fold.
Conclusions:
- The DNA origami platform offers a generalizable strategy for engineering potent antiviral agents.
- Spatially optimized nanobody presentation is key for effective viral pathogen neutralization.
- This approach presents a promising avenue for future antibody and nanobody-based drug development.
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