Scalable and sustainable manufacturing of functional DNA nanoassemblies via self-folding circular single-stranded DNA
Year: 2026
Type: article
Abstract: Functional DNA nanoassemblies (fDns) hold promise for biomedical and translational applications, but broader deployment is limited by manufacturing barriers that constrain scalability, reproducibility, and stability. Current biosynthetic approaches rely heavily on downstream enzymatic processing and purification, which dominate economic, operational, and environmental costs at scale. Here we report an integrated manufacturing strategy that combines programmed circular single-stranded DNA with bacteriophage-driven biosynthesis to enable direct production of high-quality fDns with minimal post-assembly purification. By reducing reliance on purification as a major bottleneck, this approach delivers topology-enhanced stability, high assembly efficiency, and batch reproducibility, achieving sub-gram laboratory production at ~$6 per milligram while suggesting a pathway toward scalable manufacturing. We demonstrate versatility through 11 distinct fDns, including an aptamer-functionalized construct that neutralizes SARS-CoV-2 pseudovirus and authentic Omicron variants in cellular and animal models. This work provides a cost-effective, scalable manufacturing framework for fDns, advancing their sustainable and reproducible deployment across life-science applications. Realising the potential of DNA nanomaterials for biomedical applications requires efficient manufacturing approaches. Here the authors develop a scalable bacteriophage-based method to directly produce stable, reproducible DNA nanoassemblies with minimal purification, enabling low-cost production.
Source: Nature Communications
Authors: Tingting Zhai, Siwen Liu, Dantong Lei, Ting Song, Rachel Chun-Yee Tam, Mingying Chen, Jialu Zhang, Jiangchao Qian, Chunhai Fan, Honglin Chen, Yanling Song, Hongzhou Gu
Institutions: Shanghai Jiao Tong University, Fudan University, Shanghai Stomatological Hospital, International Peace Maternity & Child Health Hospital, University of Hong Kong, Xiamen University, East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering, SJTU Asia-Pacific Graduate Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7161571080