Inhaled Nanoformulated mRNA Polyplexes for Protein Production in Lung Epithelium.

ABSTRACT: Noninvasive aerosol inhalation is an established method of drug delivery to the lung, and remains a desirable route for nucleic-acid-based therapeutics. In vitro transcribed (IVT) mRNA has broad therapeutic applicability as it permits temporal and dose-dependent control of encoded protein expression. Inhaled delivery of IVT-mRNA has not yet been demonstrated and requires development of safe and effective materials. To meet this need, hyperbranched poly(beta amino esters) (hPBAEs) are synthesized to enable nanoformulation of stable and concentrated polyplexes suitable for inhalation. This strategy achieves uniform distribution of luciferase mRNA throughout all five lobes of the lung and produces 101.2 ng g^-1 of luciferase protein 24 h after inhalation of hPBAE polyplexes. Importa

SUBMITTER: Patel AK 

PROVIDER: S-EPMC7490222 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature