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: Adriana L da Silva, Sabrina V Martini, Soraia C Abreu, Cynthia dos S Samary, Bruno L Diaz, Sandra Fernezlian, Vanessa Karen de Sá, Vera Luiza Capelozzi, Nicholas J Boylan, Rodolfo Gustavo Goya, Jung Soo Suk, Patricia R M Rocco, Justin Hanes, Marcelo M Morales
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 180 Pg. 125-33 (Apr 28 2014) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 24556417 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• DNA
• Thymic Factor, Circulating

Topics

• Airway Remodeling (genetics, immunology)
• Animals
• Asthma (genetics, immunology, pathology, therapy)
• DNA (chemistry, genetics, therapeutic use)
• Genetic Therapy
• Lung (immunology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Nanoparticles (chemistry, therapeutic use)
• Plasmids (chemistry, genetics, therapeutic use)
• Thymic Factor, Circulating (analysis, genetics)