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Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy
Open accessAbstract
Significance: Therapeutically relevant lung gene therapy is yet to be achieved. We introduce a highly translatable gene delivery platform for inhaled gene therapy based on state-of-the-art biodegradable polymers, poly(β-amino esters). The newly designed system is capable of overcoming challenging biological barriers, thereby providing robust transgene expression throughout the entire luminal surface of mouse lungs. Moreover, it provides markedly greater overall transgene expression in vivo compared with gold standard platforms, including a clinically tested system. The clinical relevance is further underscored by the excellent safety profile as well as long-term and consistent transgene expression achieved following a single and repeated administrations, respectively.
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“In recent times, biodegradable DNA NPs have shown potential for inhaled lung gene therapy, which is capable of overcoming the mucus barrier of lung airways.183”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [183]
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Metadata
- Authors
- Mastorakos, P., da Silva, A. L., Chisholm, J., Song, E., Choi, W. K., Boyle, M. P., Morales, M. M., Hanes, J., & Suk, J. S.
- Affiliations
- Johns Hopkins University (US)
- Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941902, Brazil;
- Universidade Federal do Rio de Janeiro (BR)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-06-29
- Volume
- 112
- Issue
- 28
- Pages
- 8720-8725
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4507234
- OpenAlex
- W2149239077
- Cited by
- 210
- References
- 66
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 20 · 2023: 20 · 2022: 17 · 2021: 24 · 2020: 22 · 2019: 21 · 2018: 20 · 2017: 20 · 2016: 15 · 2015: 3
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (P01 HL51811, R01 HL127413)
- Cystic Fibrosis Foundation (HANES07XX0, HANES15G0)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- DNA nanoparticles, pulmonary gene therapy, mucus barrier, poly(β-amino ester), biodegradable polymers, transgene expression, nanoparticle stability, intratracheal administration, nanoparticle toxicity
- MeSH terms
- Administration, Inhalation, Animals, Cystic Fibrosis, DNA, Mucus, Genetic Therapy, Mice, Nanoparticles
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