Automated design of scaffold-free DNA wireframe nanostructures

Abstract Computer-aided design has become common practice in DNA nanotechnology, and many programs are available that make the sophisticated design processes accessible to both the core research community and curious scientists in other fields. However, most of the design tools are committed to the...

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Main Authors: Wen Wang, Abdulmelik Mohammed, Rong Chen, Antti Elonen, Silian Chen, Mengfan Tian, Junhao Yang, Ye Xiang, Pekka Orponen, Bryan Wei
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59844-6
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author Wen Wang
Abdulmelik Mohammed
Rong Chen
Antti Elonen
Silian Chen
Mengfan Tian
Junhao Yang
Ye Xiang
Pekka Orponen
Bryan Wei
author_facet Wen Wang
Abdulmelik Mohammed
Rong Chen
Antti Elonen
Silian Chen
Mengfan Tian
Junhao Yang
Ye Xiang
Pekka Orponen
Bryan Wei
author_sort Wen Wang
collection DOAJ
description Abstract Computer-aided design has become common practice in DNA nanotechnology, and many programs are available that make the sophisticated design processes accessible to both the core research community and curious scientists in other fields. However, most of the design tools are committed to the scaffolded DNA origami method. Here we present an automated design pipeline for creating DNA wireframe nanostructures based on a scaffold-free molecular self-assembly approach. Unlike in the DNA origami method, scaffold-free designs are not built around a global backbone strand but are constituted entirely of short, locally intertwined oligonucleotides. This overcomes many limitations inherent in scaffolded nanostructure designs, most notably the size constraints imposed by the length of available scaffold strands, and the topological and algorithmic challenges of finding feasible scaffold-strand routings. In practice, this leads to simpler design flows and opens up new design possibilities. To demonstrate the flexibility and capability of our approach, we generate a variety of complex DNA wireframe designs automatically from 2D and 3D mesh models and successfully realise the respective molecular nanostructures experimentally.
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spelling doaj-art-70f1a151b83a4fe187c0bcedd26db55a2025-08-20T02:33:32ZengNature PortfolioNature Communications2041-17232025-05-011611710.1038/s41467-025-59844-6Automated design of scaffold-free DNA wireframe nanostructuresWen Wang0Abdulmelik Mohammed1Rong Chen2Antti Elonen3Silian Chen4Mengfan Tian5Junhao Yang6Ye Xiang7Pekka Orponen8Bryan Wei9School of Life Sciences, Tsinghua UniversityDepartment of Biomedical Engineering, San José State UniversitySchool of Life Sciences, Tsinghua UniversityDepartment of Computer Science, Aalto UniversityBeijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityBGI ResearchSchool of Life Sciences, Tsinghua UniversityBeijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityDepartment of Computer Science, Aalto UniversitySchool of Life Sciences, Tsinghua UniversityAbstract Computer-aided design has become common practice in DNA nanotechnology, and many programs are available that make the sophisticated design processes accessible to both the core research community and curious scientists in other fields. However, most of the design tools are committed to the scaffolded DNA origami method. Here we present an automated design pipeline for creating DNA wireframe nanostructures based on a scaffold-free molecular self-assembly approach. Unlike in the DNA origami method, scaffold-free designs are not built around a global backbone strand but are constituted entirely of short, locally intertwined oligonucleotides. This overcomes many limitations inherent in scaffolded nanostructure designs, most notably the size constraints imposed by the length of available scaffold strands, and the topological and algorithmic challenges of finding feasible scaffold-strand routings. In practice, this leads to simpler design flows and opens up new design possibilities. To demonstrate the flexibility and capability of our approach, we generate a variety of complex DNA wireframe designs automatically from 2D and 3D mesh models and successfully realise the respective molecular nanostructures experimentally.https://doi.org/10.1038/s41467-025-59844-6
spellingShingle Wen Wang
Abdulmelik Mohammed
Rong Chen
Antti Elonen
Silian Chen
Mengfan Tian
Junhao Yang
Ye Xiang
Pekka Orponen
Bryan Wei
Automated design of scaffold-free DNA wireframe nanostructures
Nature Communications
title Automated design of scaffold-free DNA wireframe nanostructures
title_full Automated design of scaffold-free DNA wireframe nanostructures
title_fullStr Automated design of scaffold-free DNA wireframe nanostructures
title_full_unstemmed Automated design of scaffold-free DNA wireframe nanostructures
title_short Automated design of scaffold-free DNA wireframe nanostructures
title_sort automated design of scaffold free dna wireframe nanostructures
url https://doi.org/10.1038/s41467-025-59844-6
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