Freeze-Drying in Sucrose Followed by Cryomilling Enables the Formulation of sa-mRNA-LNP Powders for Inhalation.

ABSTRACT: Background: Self-amplifying mRNA (sa-mRNA) represents a promising platform for vaccines and gene therapies, offering sustained protein expression at low doses through self-replication. For vaccines targeting respiratory pathogens, pulmonary delivery of sa-mRNA lipid nanoparticles (LNPs) is particularly advantageous, enabling direct delivery to the infection site and induction of mucosal immunity. Objective: In this study, we evaluated the stability of sa-mRNA-LNPs under refrigerated and frozen conditions and developed a dry powder formulation suitable for inhalation, produced by freeze-drying followed by cryomilling with leucine. Methods: sa-mRNA-LNPs formulated in HEPES buffer with 20% (w/v) sucrose were stored for up to 8 weeks as liquid or freeze-dried

SUBMITTER: Jansen EM 

PROVIDER: S-EPMC12844638 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature