Expanding Chemical Space of Nucleic Acid Nanoparticles for Tunable Antiviral‐Like Immunomodulatory Responses and Potent Adjuvant Activity
The rise of personalized medicine demands affordable biomaterials with tunable physicochemical properties, biological activities, and immune responses. We introduce a nucleic acid nanoparticle (NANP)-based platform designed to engage with the human immune system in a controllable manner. By varying the chemical composition while keeping the architectural parameters constant, we identified key factors that influence the immunorecognition and stability of NANPs. Chemical modifications provide additive functional regulation, while pairing NANPs with different delivery agents further enhances their immunomodulatory capabilities. Specific compositions boost T cell effector functions, promote B cell proliferation, and activate innate immune populations in human peripheral blood mononuclear cells. The resulting interferon responses and immune signatures mimic those triggered by viral infections. Notably, in vivo studies demonstrate that NANPs function as efficiently as traditional clinically used adjuvants, without increasing the risk of autoimmunity. This suggests that NANPs are a safe and effective tool for immunotherapy with promise for developing formulations targeting cancer and infectious diseases.
Authors
- Justin R. Halman (ORCID: https://orcid.org/0000-0003-2281-9909)
- Jian Wang (ORCID: https://orcid.org/0000-0001-7768-2802)
- Morgan Chandler (ORCID: https://orcid.org/0000-0003-3078-6000)
- Nikolay V. Dokholyan
- Yongmei Zhao (ORCID: https://orcid.org/0000-0001-8639-1791)
- Shaojun Xie (ORCID: https://orcid.org/0000-0002-6719-9814)
- Kirill A. Afonin (ORCID: https://orcid.org/0000-0002-6917-3183)
- Hannah S. Newton (ORCID: https://orcid.org/0000-0002-6368-0803)
- Laxmi Pandey (ORCID: https://orcid.org/0000-0002-6066-6723)
- Marina A. Dobrovolskaia (ORCID: https://orcid.org/0000-0002-4233-9227)
- Elijah F. Edmondson (ORCID: https://orcid.org/0000-0002-6106-3705)
- Yasmine Radwan (ORCID: https://orcid.org/0000-0002-8383-9033)
- Simone Difilippantonio (ORCID: https://orcid.org/0000-0002-8234-1559)
- Edward Cedrone
- Chelsea Sanders (ORCID: https://orcid.org/0000-0001-8042-4783)
- Martin Panigaj (ORCID: https://orcid.org/0000-0002-0940-8737)
- Bao Xuan Tran (ORCID: https://orcid.org/0009-0007-3905-6908)
- Barry W. Neun
- Meni Wanunu
- Phong Nguyen
- Yelixza I. Avilla
- Stephanie Smith
Institutions
- University of North Carolina at Charlotte (US)
- Northeastern University (US)
- Frederick National Laboratory for Cancer Research (US)
- Biological Mimetics (United States) (US)
- University of Virginia (US)
Publication Details
- Journal
- Advanced Functional Materials
- Published
- 2026-01-07
- DOI
- https://doi.org/10.1002/adfm.202515585
- Citations
- 1
- Primary Topic
- RNA Interference and Gene Delivery
- Type
- article
- Field-Weighted Citation Impact
- 22.24
Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- National Cancer Institute
- National Institute of General Medical Sciences