Tetrafunctional Block Copolymers Promote Lung Gene Transfer in Newborn Piglets.
gene therapy
lungs
newborn pigs
non-viral vector
tetrafunctional block copolymers
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
07 Jun 2019
07 Jun 2019
Historique:
received:
04
12
2018
revised:
15
02
2019
accepted:
15
02
2019
pubmed:
22
3
2019
medline:
22
3
2019
entrez:
22
3
2019
Statut:
ppublish
Résumé
Tetrafunctional block copolymers are molecules capable of complexing DNA. Although ineffective in vitro, studies in mice have shown that the tetrafunctional block copolymer 704 is a more efficient lung gene transfer agent than the cationic liposome GL67A, previously used in a phase II clinical trial in cystic fibrosis patients. In the present study, we compared the gene transfer capacity of the 704-DNA formulation and a cationic liposome-DNA formulation equivalent to GL67A in a larger-animal model, the newborn piglet. Our results indicate an efficacy of the 704-DNA formulation well above one order of magnitude higher than that of the cationic liposome-DNA formulation, with no elevated levels of interleukin-6 (IL-6), taken as a marker of inflammation. Transgene expression was heterogeneous within lung lobes, with expression levels that were below the detection threshold in some samples, while high in other samples. This heterogeneity is likely to be due to the bolus injection procedure as well as to the small volume of injection. The present study highlights the potential of tetrafunctional block copolymers as non-viral vectors for lung gene therapy.
Identifiants
pubmed: 30897407
pii: S2162-2531(19)30046-0
doi: 10.1016/j.omtn.2019.02.016
pmc: PMC6426709
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
186-193Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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