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...
Guardado en:
Autores principales: | , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Nature Portfolio
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/f0fc16a29af14728a68a1da1325adeb2 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:f0fc16a29af14728a68a1da1325adeb2 |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT rebeccamlegere safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent AT noahdcohen safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent AT cristinapoveda safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent AT jocelynembray safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent AT rolabarhoumi safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent AT josephaszule safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent AT andresdelaconchabermejillo safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent AT angelaibordin safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent AT jeroenpollet safeandeffectiveaerosolizationofinvitrotranscribedmrnatotherespiratorytractepitheliumofhorseswithoutatransfectionagent |
_version_ |
1718392177536532480 |