Format

Send to

Choose Destination
J Control Release. 2014 Apr 28;180:125-33. doi: 10.1016/j.jconrel.2014.02.010. Epub 2014 Feb 17.

DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma.

Author information

1
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.
2
Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
3
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
4
Laboratory of Immunology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
5
Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
6
Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, USA; The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, USA.
7
Institute for Biochemical Research at La Plata (INIBIOLP), and Histology and Embryology, Faculty of Medicine, National University of La Plata, La Plata, Argentina.
8
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.
9
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.
10
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.

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.

KEYWORDS:

Allergy gene therapy; DNA nanoparticles; Lung remodeling; Thymulin

PMID:
24556417
PMCID:
PMC3992277
DOI:
10.1016/j.jconrel.2014.02.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center