Abstract
Generative models that have advanced inverse design in protein engineering can be extended to DNA origami to explore broader design spaces enabling complex geometries and functions for emerging nanotechnologies. However, progress in generative DNA origami design has been limited by the lack of large, standardized structural datasets containing structural information. To address this challenge, we introduce a diffusion-based generative design framework trained on simulated equilibrium conformations obtained using a multiscale computational model. Given user-defined target geometries, our model produces physically plausible DNA origami designs through guided diffusion sampling and strand routing, with integrated structure prediction for quantitative evaluation. Among more than 100 generated candidates, selected structures are experimentally validated, demonstrating proper folding and functional behaviors such as auxetic transformation and modular assembly. Our results highlight the potential of generative modeling for complex DNA origami design, expanding the accessible design space and facilitating the creation of sophisticated, reconfigurable architectures.
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D.-N.K. discloses support for the research of this work from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [RS-2024-00346176], the National Supercomputing Center with supercomputing resources including technical support [KSC-2024-CHA-0003], and Youlchon Foundation (Nongshim Corporation and affiliated companies) in Korea. C.L. discloses support for the research of this work from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [RS-2026-25490531]. The remaining authors declare no relevant funding.
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D.-N.K., C.L., C.T.-Q., and K.J. are co-inventors on a patent application filed with the Ministry of Intellectual Property (MOIP) of the Republic of Korea. The application covers the generative diffusion model framework for DNA nanostructure design as described in this manuscript. The application was filed by Seoul National University R&DB Foundation, Korea, and Youlchon Foundation (Nongshim Corporation and affiliated companies), Korea (No. 10-2026-0067822) and is currently pending. The remaining authors declare no competing interests.
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Truong-Quoc, C., Jeon, K., Kim, J. et al. De novo design of DNA origami with a generative diffusion model. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73578-z
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DOI: https://doi.org/10.1038/s41467-026-73578-z
