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Self-assembled peptide–poloxamine nanoparticles enable in vitro and in vivo genome restoration for cystic fibrosis
Abstract
Developing safe and efficient non-viral delivery systems remains a major challenge for in vivo applications of gene therapy, especially in cystic fibrosis. Unlike conventional cationic polymers or lipids, the emerging poloxamine-based copolymers display promising in vivo gene delivery capabilities. However, poloxamines are invalid for in vitro applications and their in vivo transfection efficiency is still low compared with viral vectors. Here, we show that peptides developed by modular design approaches can spontaneously form compact and monodisperse nanoparticles with poloxamines and nucleic acids via self-assembly. Both messenger RNA and plasmid DNA expression mediated by peptide-poloxamine nanoparticles are greatly boosted in vitro and in the lungs of cystic fibrosis mice with negligible toxicity. Peptide-poloxamine nanoparticles containing integrating vectors enable successful in vitro and in vivo long-term restoration of cystic fibrosis transmembrane conductance regulator deficiency with a safe integration profile. Our dataset provides a new framework for designing non-viral gene delivery systems qualified for in vivo genetic modifications.
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“After three-time i.t. administration, CFTR expression lasted for 18 weeks in CF mice and the level was similar to that of the wild type group.”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [45]
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“Meanwhile, lung pathohistological sections indicated no visible signs of inflammatory infiltrates and blood sample analysis showed a normal level of white blood cells.[45]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [45]
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Metadata
- Authors
- Guan, S., Munder, A., Hedtfeld, S., Braubach, P., Glage, S., Zhang, L., Lienenklaus, S., Schultze, A., Hasenpusch, G., Garrels, W., Stanke, F., Miskey, C., Johler, S. M., Kumar, Y., Tümmler, B., Rudolph, C., Ivics, Z., & Rosenecker, J.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Medizinische Hochschule Hannover (DE)
- Ethris (Germany) (DE)
- Paul Ehrlich Institut (DE)
- GATC Biotech (Germany) (DE)
- Corresponding author
- Rosenecker, Joseph
- ORCID
- Venue
- Nature Nanotechnology
- Published
- 2019-01-28
- Volume
- 14
- Issue
- 3
- Pages
- 287-297
- ISSN
- 1748-3387 (ISSN-L)
- 1748-3395
- OpenAlex
- W2914518223
- Cited by
- 130
- References
- 51
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 19 · 2023: 19 · 2022: 21 · 2021: 13 · 2020: 16 · 2019: 10
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Nanotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- cystic fibrosis, poloxamine, self-assembly, non-viral gene delivery, gene therapy, CFTR, plasmid transfection, mRNA delivery, integrating vectors, in vivo transfection, lung gene delivery
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Cystic Fibrosis, Ethylenediamines, Gene Expression Regulation, Humans, Luciferases, Peptides, RNA, Messenger, Genome, Genes, Reporter, Cystic Fibrosis Transmembrane Conductance Regulator, Transgenes, Mice, Nanoparticles
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