RNA‐DNA Fusomer Fibers With Customizable Physicochemical, Mechanical, and Biological Properties for Next‐Generation Therapeutics
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.
Authors
- Yelixza I. Avila (ORCID: https://orcid.org/0000-0001-5167-8071)
- Morgan Chandler (ORCID: https://orcid.org/0000-0003-3078-6000)
- Ian Marriott (ORCID: https://orcid.org/0000-0002-4005-3487)
- Elizabeth Skelly (ORCID: https://orcid.org/0000-0003-1157-0845)
- Kirill A. Afonin (ORCID: https://orcid.org/0000-0002-6917-3183)
- Marina A. Dobrovolskaia (ORCID: https://orcid.org/0000-0002-4233-9227)
- Hemani Chhabra (ORCID: https://orcid.org/0009-0008-3211-5693)
- Yasmine Radwan (ORCID: https://orcid.org/0000-0002-8383-9033)
- Laura P. Rebolledo (ORCID: https://orcid.org/0009-0007-7424-4568)
- Lauren Rackley
- Renata de Freitas Saito (ORCID: https://orcid.org/0000-0002-4625-6082)
- Roger Chammas (ORCID: https://orcid.org/0000-0003-0342-8726)
- Alexander Lushnikov (ORCID: https://orcid.org/0009-0009-8313-308X)
- Alexey V. Krasnoslobodtsev (ORCID: https://orcid.org/0000-0003-1457-514X)
- Tatiane Katsue Furuya
- Julio Navas Hernandez
- Edward Cedrone
- Ana Luiza Lomba
- Aleksei Aksimentiev
- Laxmi K. Pandey
- Meni Wanunu
- Da Shi
Institutions
- University of North Carolina at Charlotte (US)
- University of Nebraska at Omaha (US)
- Northeastern University (US)
- University of Illinois Urbana-Champaign (US)
- Universidade de São Paulo (BR)
- Instituto do Câncer do Estado de São Paulo (BR)
- Frederick National Laboratory for Cancer Research (US)
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- Biological Mimetics (United States) (US)
Publication Details
- Journal
- Small
- Published
- 2026-06-09
- DOI
- https://doi.org/10.1002/smll.202600078
- Primary Topic
- Advanced biosensing and bioanalysis techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- Division of Molecular and Cellular Biosciences