title: Polyethyleneimine and DNA nanoparticles-based gene therapy for acute lung injury.
abstract: Acute lung injury (ALI) is a devastating clinical syndrome causing a substantial mortality, but to date without any effective pharmacological management in clinic. Here, we tested whether nanoparticles based on polyethylenimine (PEI) and DNA could be a potential treatment. In mouse model of ALI induced by lipopolysaccharide (LPS) (10mg/kg), intravenous injection of PEI/DNA mediated a rapid (in 6h) and short-lived transgene expression in lung, with alveolar epithelial cells as major targets. When β2-Adrenergic Receptor (β2AR) was applied as therapeutic gene, PEI/β2AR treatment significantly attenuated the severity of ALI, including alveolar fluid clearance, lung water content, histopathology, bronchioalveolar lavage cellularity, protein concentration, and inflammatory cytokines in mice with pre-existing ALI. In high-dose LPS (40 mg/kg)-induced ALI, post-injury treatment of PEI/β2AR significantly improved the 5-day survival of mice from 28% to 64%. These data suggest that PEI/DNA nanoparticles could be an effective agent in future clinical application for ALI treatment.
  
  
  BACKGROUND
  In this novel study, PEI/DNA nanoparticles are presented as an effective agent for the treatment of the devastating and currently untreatable syndrome of acute lung injury, using a rodent model system.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taiwan; Institute of Microbiology and Immunology, National Yang-Ming University, Taiwan.
authors.forename: Erh-Hsuan
authors.initials: EH
authors.lastname: Lin
authors.forename: Hsiang-Yi
authors.initials: HY
authors.lastname: Chang
authors.forename: Shauh-Der
authors.initials: SD
authors.lastname: Yeh
authors.forename: Kuang-Yao
authors.initials: KY
authors.lastname: Yang
authors.forename: Huei-Sin
authors.initials: HS
authors.lastname: Hu
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Wu
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D000818:Animals; D004247:DNA / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011943:Receptors, Adrenergic, beta / Q000235:genetics*
chemical_list: D011943:Receptors, Adrenergic, beta; D011094:Polyethyleneimine; D004247:DNA
keywords: Gene therapy; LPS-induced acute lung injury; Lung epithelium; Nanoparticle; β2-Adrenergic receptor