Inhalable dry powder mRNA vaccines based on extracellular vesicles.
COVID-19
dry powder inhalation
exosomes
extracellular vesicles
lung
mRNA vaccine
nonhuman primate
spike protein
Journal
Matter
ISSN: 2590-2385
Titre abrégé: Matter
Pays: United States
ID NLM: 101749591
Informations de publication
Date de publication:
07 Sep 2022
07 Sep 2022
Historique:
received:
02
02
2022
revised:
29
04
2022
accepted:
07
06
2022
pubmed:
19
7
2022
medline:
19
7
2022
entrez:
18
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35847197
doi: 10.1016/j.matt.2022.06.012
pii: S2590-2385(22)00307-1
pmc: PMC9272513
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2960-2974Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL149940
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL154154
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL164998
Pays : United States
Organisme : NIH HHS
ID : T35 OD011070
Pays : United States
Informations de copyright
© 2022 Elsevier Inc.
Déclaration de conflit d'intérêts
North Carolina State University has filed a patent on the technologies related to this study. K.C. is an equity holder and consultant of Xsome Biotech, Inc. Xsome has entered an exclusive license agreement with North Carolina State University.
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