CFTR and dystrophin encoding plasmids carrying both luciferase reporter gene, nuclear import specific sequences and triple helix sites.
CFTR
DNA constructs
Dystrophin
Tissue specific promoter
Triple helix
Journal
Plasmid
ISSN: 1095-9890
Titre abrégé: Plasmid
Pays: United States
ID NLM: 7802221
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
07
11
2022
revised:
26
04
2023
accepted:
16
05
2023
medline:
28
8
2023
pubmed:
20
5
2023
entrez:
19
5
2023
Statut:
ppublish
Résumé
Duchenne Muscular Dystrophy and Cystic Fibrosis are two major monogenetic diseases which could be treated by non-viral gene therapy. For this purpose, plasmid DNA (pDNA) coding for the functional genes requires its equipment with signal molecules favouring its intracellular trafficking and delivery in the nucleus of the target cells. Here, two novel constructions of large pDNAs encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and full-length dystrophin (DYS) genes are reported. The expression of CFTR and DYS genes are driven respectively by the hCEF1 airway epithelial cells and spc5-12 muscle cells specific promoter. Those pDNAs encode also the luciferase reporter gene driven by the CMV promoter to evaluate gene delivery in animals by bioluminescence. In addition, oligopurine • oligopyrimidine sequences are inserted to enable equipment of pDNAs with peptides conjugated with a triple helix forming oligonucleotide (TFO). Furthermore, specific κB sequences are also inserted to promote their NFκB-mediated nuclear import. pDNA constructions are reported; transfection efficiency, tissue specific expression of CFTR and dystrophin in target cells, and triple helix formation are demonstrated. These plasmids are tools of interest to develop non-viral gene therapy of Cystic Fibrosis and Duchenne Muscular Dystrophy.
Identifiants
pubmed: 37207938
pii: S0147-619X(23)00017-3
doi: 10.1016/j.plasmid.2023.102686
pii:
doi:
Substances chimiques
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
DNA
9007-49-2
Dystrophin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102686Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Patrick Midoux reports financial support was provided by Association Française contre les Myopathies. Patrick Midoux reports financial support was provided by Vaincre la mucoviscidose. Delphine Maze reports financial support was provided by Vaincre la mucoviscidose. Delphine Maze reports financial support was provided by Association Française contre les Myopathies. Caroline Girardin reports financial support was provided by University of Orléans and Région Centre Val de Loire.