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

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

Research output: Contribution to journalArticlepeer-review

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 27 days 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.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalJournal of Controlled Release
Volume180
Issue number1
DOIs
StatePublished - Apr 28 2014

Keywords

  • Allergy gene therapy
  • DNA nanoparticles
  • Lung remodeling
  • Thymulin

ASJC Scopus subject areas

  • Pharmaceutical Science

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