Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung.
Journal
Nature materials
ISSN: 1476-4660
Titre abrégé: Nat Mater
Pays: England
ID NLM: 101155473
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
16
09
2021
accepted:
11
10
2022
pubmed:
29
11
2022
medline:
7
3
2023
entrez:
28
11
2022
Statut:
ppublish
Résumé
Messenger RNA has now been used to vaccinate millions of people. However, the diversity of pulmonary pathologies, including infections, genetic disorders, asthma and others, reveals the lung as an important organ to directly target for future RNA therapeutics and preventatives. Here we report the screening of 166 polymeric nanoparticle formulations for functional delivery to the lungs, obtained from a combinatorial synthesis approach combined with a low-dead-volume nose-only inhalation system for mice. We identify P76, a poly-β-amino-thio-ester polymer, that exhibits increased expression over formulations lacking the thiol component, delivery to different animal species with varying RNA cargos and low toxicity. P76 allows for dose sparing when delivering an mRNA-expressed Cas13a-mediated treatment in a SARS-CoV-2 challenge model, resulting in similar efficacy to a 20-fold higher dose of a neutralizing antibody. Overall, the combinatorial synthesis approach allowed for the discovery of promising polymeric formulations for future RNA pharmaceutical development for the lungs.
Identifiants
pubmed: 36443576
doi: 10.1038/s41563-022-01404-0
pii: 10.1038/s41563-022-01404-0
doi:
Substances chimiques
RNA, Messenger
0
Polymers
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
369-379Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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