Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent

Abstract 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 safe...

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Autores principales:	Rebecca M. Legere, Noah D. Cohen, Cristina Poveda, Jocelyne M. Bray, Rola Barhoumi, Joseph A. Szule, Andrés de la Concha-Bermejillo, Angela I. Bordin, Jeroen Pollet
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f0fc16a29af14728a68a1da1325adeb2
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spelling	oai:doaj.org-article:f0fc16a29af14728a68a1da1325adeb22021-12-02T14:01:33ZSafe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent10.1038/s41598-020-79855-12045-2322https://doaj.org/article/f0fc16a29af14728a68a1da1325adeb22021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79855-1https://doaj.org/toc/2045-2322Abstract 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.Rebecca M. LegereNoah D. CohenCristina PovedaJocelyne M. BrayRola BarhoumiJoseph A. SzuleAndrés de la Concha-BermejilloAngela I. BordinJeroen PolletNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rebecca M. Legere Noah D. Cohen Cristina Poveda Jocelyne M. Bray Rola Barhoumi Joseph A. Szule Andrés de la Concha-Bermejillo Angela I. Bordin Jeroen Pollet Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent
description	Abstract 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.
format	article
author	Rebecca M. Legere Noah D. Cohen Cristina Poveda Jocelyne M. Bray Rola Barhoumi Joseph A. Szule Andrés de la Concha-Bermejillo Angela I. Bordin Jeroen Pollet
author_facet	Rebecca M. Legere Noah D. Cohen Cristina Poveda Jocelyne M. Bray Rola Barhoumi Joseph A. Szule Andrés de la Concha-Bermejillo Angela I. Bordin Jeroen Pollet
author_sort	Rebecca M. Legere
title	Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent
title_short	Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent
title_full	Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent
title_fullStr	Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent
title_full_unstemmed	Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent
title_sort	safe and effective aerosolization of in vitro transcribed mrna to the respiratory tract epithelium of horses without a transfection agent
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f0fc16a29af14728a68a1da1325adeb2
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Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent

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