{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lian L"],"funding":["HHS | NIH (NIH)"],"pagination":["e2511483123"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12913010"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["123(7)"],"pubmed_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"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Lipid nanoparticle GM-CSF replacement for autoimmune pulmonary alveolar proteinosis."],"pmcid":["PMC12913010"],"funding_grant_id":["U19AI171421"],"pubmed_authors":["Gentry K","Jang B","Guerrero-Ferreira RC","Parihar VC","Kim H","Zenhausern R","Calkins R","Vanover D","Lian L","Dahlman JE","Radmand A","Huayamares SG","Shakked A","Santangelo PJ","Schrader Echeverri E"],"additional_accession":[]},"is_claimable":false,"name":"Lipid nanoparticle GM-CSF replacement for autoimmune pulmonary alveolar proteinosis.","description":"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","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-16T06:55:30.134Z","creation":"2026-07-09T13:10:37.395Z"},"accession":"S-EPMC12913010","cross_references":{"pubmed":["41671176"],"doi":["10.1073/pnas.2511483123"]}}