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Inhalable dry powder mRNA vaccines based on extracellular vesicles
Open accessAbstract
Respiratory diseases are a global burden, with millions of deaths attributed to pulmonary illnesses and dysfunctions. Therapeutics have been developed, but they present major limitations regarding pulmonary bioavailability and product stability. To circumvent such limitations, we developed room-temperature-stable inhalable lung-derived extracellular vesicles or exosomes (Lung-Exos) as mRNA and protein drug carriers. Compared with standard synthetic nanoparticle liposomes (Lipos), Lung-Exos exhibited superior distribution to the bronchioles and parenchyma and are deliverable to the lungs of rodents and nonhuman primates (NHPs) by dry powder inhalation. In a vaccine application, severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein encoding mRNA-loaded Lung-Exos (S-Exos) elicited greater immunoglobulin G (IgG) and secretory IgA (SIgA) responses than its loaded liposome (S-Lipo) counterpart. Importantly, S-Exos remained functional at room-temperature storage for one month. Our results suggest that extracellular vesicles can serve as an inhaled mRNA drug-delivery system that is superior to synthetic liposomes.
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“One of the key benefits of exosomes is their ability to express surface proteins and receptors of their donor cells, allowing them to target recipient cells within the same tissue effectively. For example, lung spheroid cell-derived exosomes can deliver vaccines directly to lung tissue [82].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [82]
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Metadata
- Authors
- Popowski, K. D., Moatti, A., Scull, G., Silkstone, D., Lutz, H., López de Juan Abad, B., George, A., Belcher, E., Zhu, D., Mei, X., Cheng, X., Cislo, M., Ghodsi, A., Cai, Y., Huang, K., Li, J., Brown, A. C., Greenbaum, A., Dinh, P.-U. C., & Cheng, K.
- Affiliations
- North Carolina State University (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Dinh, Phuong-Uyen C.
- Cheng, Ke
- ORCID
- Venue
- Matter
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 5
- Issue
- 9
- Pages
- 2960-2974
- ISSN
- 2590-2385 (ISSN-L)
- PMC
- PMC9272513
- OpenAlex
- W4285008938
- Cited by
- 218
- References
- 50
- Citations by year
- 2026: 33 · 2025: 62 · 2024: 59 · 2023: 55 · 2022: 8
- FWCI
- 15.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Matter (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL164998, HL137093, HL144002, HL149940, HL146701, HL146153, HL147357, HL123920)
- American Heart Association (19EIA34660286, T32GM133393, 18TPA34230092)
- College of Veterinary Medicine, North Carolina State University
- North Carolina State University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- extracellular vesicles, exosomes, mRNA vaccines, dry powder inhalation, pulmonary drug delivery, liposomes, SARS-CoV-2 spike protein, secretory IgA, IgG antibody response, room-temperature stability, non-human primates
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