journal article·2026-06-09Open access

RNA‐DNA Fusomer Fibers With Customizable Physicochemical, Mechanical, and Biological Properties for Next‐Generation Therapeutics

Yasmine Radwan, Laura P. Rebolledo, Yelixza I. Avila, Elizabeth Skelly, Lauren Rackley, Julio Navas Hernandez, Renata de Freitas Saito, Laxmi K. Pandey, Hemani Chhabra, Alexander J. Lushnikov, Tatiane Katsue Furuya, Ana Luiza Lomba, Da Shi, Edward Cedrone, Ian Marriott, Morgan R. Chandler, Meni Wanunu, Aleksei Aksimentiev, Alexey V. Krasnoslobodtsev, Roger Chammas, Marina A. Dobrovolskaia, Kirill A. Afonin

Abstract

ABSTRACT We introduce RNA‐DNA fusomers, a new class of chemically synthesized oligonucleotides that combine the versatile properties of RNA and DNA within a single sequence and self‐assemble into higher‐order functional structures via a simple one‐pot annealing reaction. This hybrid platform allows precise customization with therapeutic nucleic acids, offering tunable physicochemical, mechanical, and immunological properties, cost‐effective production, and the capacity to integrate biological functionalities intrinsic to both RNA and DNA. The modular architecture of fusomers enables straightforward optimization for diverse biomedical applications, including gene silencing, anti‐inflammatory therapy, anticoagulation, antibacterial activity, and protein biosensing. We demonstrate efficient delivery and intracellular modulation by fusomers in multiple model systems, including human peripheral blood mononuclear cells isolated from healthy human donors and 3D organ‐on‐a‐chip models. Molecular dynamics simulations further elucidate the structural behavior of fusomers and their intended interactions with protein targets. Collectively, these findings position fusomers as a next‐generation therapeutic platform with broad transformative potential.
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Research context

OpenAlex topics: Advanced biosensing and bioanalysis techniques · DNA and Nucleic Acid Chemistry · RNA Interference and Gene Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Chemistry and Nanoscale Science Program Department of Chemistry University of North Carolina Charlotte Charlotte North Carolina USA

Department of Physics University of Nebraska Omaha Omaha Nebraska USA

Center for Translational Research in Oncology (LIM24) Instituto do Câncer do Estado de São Paulo (ICESP) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) São Paulo SP Brazil

Comprehensive Center for Precision Oncology Universidade de São Paulo São Paulo SP Brazil

Department of Physics Northeastern University Boston Massachusetts USA

Beckman Institute for Advanced Science and Technology University of Illinois at Urbana‐Champaign Urbana Illinois USA

Nanotechnology Characterization Laboratory Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute Frederick Maryland USA

Department of Biological Sciences University of North Carolina at Charlotte Charlotte North Carolina USA

Center for Innovation Translational Research and Applications of Nanostructured Systems (CITRANS) University of North Carolina at Charlotte Charlotte North Carolina USA

MIMETAS US INC Gaithersburg Maryland USA

Department of Physics University of Illinois at Urbana‐Champaign Urbana Illinois USA

Funding

National Institutes of Health · U.S. Department of Health and Human Services · Division of Molecular and Cellular Biosciences

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