Lipid nanoparticle GM-CSF replacement for autoimmune pulmonary alveolar proteinosis.

ABSTRACT: Granulocyte-macrophage colony-stimulating factor (GM-CSF) deficiency drives autoimmune pulmonary alveolar proteinosis (aPAP), a disease characterized by impaired macrophage-mediated clearance of pulmonary surfactants. Clinical data suggest that inhaled recombinant GM-CSF reduces symptoms in aPAP patients, providing a rationale for mRNA-based GM-CSF replacement therapies. However, these require effective mRNA delivery after nebulization. Here, we report the iterative in vivo design of a lipid nanoparticle, named nebulized lung delivery 2 (NLD2), that efficiently delivers mRNA after nebulization. NLD2 carrying GM-CSF mRNA transfected alveolar macrophages in vivo, leading to interleukin-10 pathway activation and subsequent surfactant lipoprotein clearance. In a preclinical disease model of aP

SUBMITTER: Lian L 

PROVIDER: S-EPMC12913010 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature