title: DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma.
abstract: Thymulin has been shown to present anti-inflammatory and anti-fibrotic properties in experimental lung diseases. We hypothesized that a biologically active thymulin analog gene, methionine serum thymus factor, delivered by highly compacted DNA nanoparticles may prevent lung inflammation and remodeling in a mouse model of allergic asthma. The DNA nanoparticles are composed of a single molecule of plasmid DNA compacted with block copolymers of poly-L-lysine and polyethylene glycol (CK30PEG), which have been found safe in a human phase I/II clinical trial. Thymulin plasmids were detected in the lungs of ovalbumin-challenged asthmatic mice up to 27days after administration of DNA nanoparticles carrying thymulin plasmids. A single dose of DNA nanoparticles carrying thymulin plasmids prevented lung inflammation, collagen deposition and smooth muscle hypertrophy in the lungs of a murine model of ovalbumin-challenged allergic asthma, leading to improved lung mechanics. In the present model of chronic allergic asthma, highly compacted DNA nanoparticles using thymulin analog gene modulated the inflammatory and remodeling processes improving lung mechanics.
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Adriana L
authors.initials: AL
authors.lastname: da Silva
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sabrina V
authors.initials: SV
authors.lastname: Martini
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Soraia C
authors.initials: SC
authors.lastname: Abreu
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Cynthia dos S
authors.initials: Cdos S
authors.lastname: Samary
authors.affiliation: Laboratory of Immunology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Diaz
authors.affiliation: Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fernezlian
authors.affiliation: Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Vanessa Karen
authors.initials: VK
authors.lastname: de Sá
authors.affiliation: Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
authors.affiliation: Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, USA; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Boylan
authors.affiliation: Institute for Biochemical Research at La Plata (INIBIOLP), and Histology and Embryology, Faculty of Medicine, National University of La Plata, La Plata, Argentina.
authors.forename: Rodolfo Gustavo
authors.initials: RG
authors.lastname: Goya
authors.affiliation: The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Suk
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Patricia R M
authors.initials: PR
authors.lastname: Rocco
authors.affiliation: Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, USA; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, USA; Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: hanes@jhmi.edu.
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: mmorales@biof.ufrj.br.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
mesh_terms: D056151:Airway Remodeling / Q000235:genetics / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D015316:Genetic Therapy; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D010957:Plasmids / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D013935:Thymic Factor, Circulating / Q000032:analysis / Q000235:genetics*
chemical_list: D004247:DNA; D013935:Thymic Factor, Circulating
keywords: Allergy gene therapy; DNA nanoparticles; Lung remodeling; Thymulin