DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma
Open accessAbstract
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.
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A single instillation of pDNA NP-mediated thymulin improved lung function for up to 27 days by preventing lung inflammation, muscle hypertrophy, and collagen deposition.
“A single instillation of pDNA NP-mediated thymulin improved lung function for up to 27 days by preventing lung inflammation, muscle hypertrophy, and collagen deposition.182”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [182]
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- Authors
- da Silva, A. L., Martini, S. V., Abreu, S. C., Samary, C. D. S., Diaz, B. L., Fernezlian, S., de Sá, V. K., Capelozzi, V. L., Boylan, N. J., Goya, R. G., Suk, J. S., Rocco, P. R. M., Hanes, J., & Morales, M. M.
- Affiliations
- Universidade Federal do Rio de Janeiro (BR)
- Universidade de São Paulo (BR)
- Johns Hopkins University (US)
- Biochemistry Research Institute of La Plata (AR)
- Corresponding author
- Hanes, Justin
- Morales, Marcelo M.
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 180
- Pages
- 125-133
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC3992277
- OpenAlex
- W2058389543
- Cited by
- 61
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 11 · 2022: 7 · 2021: 9 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 3
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Funders
- 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
- European Community's Seventh Framework Programme (FP7-2007-2013)
- National Institutes of Health (R01EB003558, P01HL51811)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- thymulin, gene therapy, DNA nanoparticles, airway remodeling, allergic asthma, poly-L-lysine, polyethylene glycol, ovalbumin challenge, lung inflammation, collagen deposition, smooth muscle hypertrophy, lung mechanics, antifibrotic therapy
- MeSH terms
- Animals, Asthma, DNA, Lung, Male, Mice, Inbred BALB C, Plasmids, Thymic Factor, Circulating, Genetic Therapy, Mice, Nanoparticles, Airway Remodeling
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