Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent
Open accessAbstract
Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (PEI)-derived transfection agent. We were able to safely and effectively transfect the bronchial epithelium of foals using naked mRNA (i.e., mRNA formulated in a sodium citrate buffer without a delivery vehicle). Endoscopic examination of the bronchial tree and histology of mucosal biopsies indicated no gross or microscopic adverse effects of the transfection. Our data suggest that mRNA administered by an atomization device eliminates the need for chemical transfection agents, which can reduce the cost and the safety risks of delivering mRNA to the respiratory tract of animals and humans.
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COVID-19 mRNA vaccines: Platforms and current developments
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- Authors
- Legere, R. M., Cohen, N. D., Poveda, C., Bray, J. M., Barhoumi, R., Szule, J. A., de la Concha-Bermejillo, A., Bordin, A. I., & Pollet, J.
- Affiliations
- Texas A&M University (US)
- Baylor College of Medicine (US)
- Corresponding author
- Cohen, Noah D.
- Pollet, Jeroen
- ORCID
- Venue
- Scientific Reports
- Published
- 2021-01-11
- Volume
- 11
- Issue
- 1
- Pages
- 371-371
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7801524
- OpenAlex
- W3120368938
- Cited by
- 20
- References
- 46
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 7 · 2022: 3 · 2021: 2
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Department of Large Animal Clinical Sciences, Texas A
- Grayson-Jockey Club Research Foundation
- Link Equine Research Endowment, Texas A
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- in vitro transcribed mRNA, aerosol delivery, transfection agents, polyethyleneimine, bronchial epithelium, horses, foals, respiratory tract, mRNA translation, mRNA vaccines, mRNA therapeutics, mucosal delivery
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Drug Carriers, Epithelial Cells, Female, Horses, Lung, Nebulizers and Vaporizers, Polyethyleneimine, RNA, Messenger, Transcription, Genetic, Transfection, Drug Delivery Systems, Vaccines, DNA, Respiratory Mucosa, Nasal Sprays
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