TY - JOUR
T1 - DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma
AU - Da Silva, Adriana L.
AU - Martini, Sabrina V.
AU - Abreu, Soraia C.
AU - Samary, Cynthia Dos S.
AU - Diaz, Bruno L.
AU - Fernezlian, Sandra
AU - De Sá, Vanessa Karen
AU - Capelozzi, Vera Luiza
AU - Boylan, Nicholas J.
AU - Goya, Rodolfo Gustavo
AU - Suk, Jung Soo
AU - Rocco, Patricia R.M.
AU - Hanes, Justin
AU - Morales, Marcelo M.
N1 - Funding Information:
The authors express their gratitude to Andre Benedito da Silva for animal care and Ana Lucia Neves da Silva for her help with microscopy. This work was supported by the following: Centers of Excellence Program (PRONEX-FAPERJ) , Brazilian Council for Scientific and Technological Development (CNPq) , Carlos Chagas Filho , Rio de Janeiro State Research Supporting Foundation (FAPERJ) , Coordination for the Improvement of Higher Education Personnel (CAPES) , São Paulo State Research Supporting Foundation (FAPESP) , INCT-INOFAR , the European Community's Seventh Framework Programme (TARKINAID, FP7-2007-2013 ) and the National Institutes of Health ( R01EB003558 and P01HL51811 ).
PY - 2014/4/28
Y1 - 2014/4/28
N2 - 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.
AB - 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.
KW - Allergy gene therapy
KW - DNA nanoparticles
KW - Lung remodeling
KW - Thymulin
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U2 - 10.1016/j.jconrel.2014.02.010
DO - 10.1016/j.jconrel.2014.02.010
M3 - Article
C2 - 24556417
AN - SCOPUS:84896135150
SN - 0168-3659
VL - 180
SP - 125
EP - 133
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -