Title :

Use of 2,6-diaminopurine as a potent suppressor of UGA premature stop codons in cystic fibrosis

Author(s) :

Leroy, Catherine [Auteur]
Spelier, Sacha [Auteur]
Essonghe, Nadège Charlene [Auteur]
Poix, Virginie [Auteur]
Kong, Rebekah [Auteur]
Gizzi, Patrick [Auteur]
Bourban, Claire [Auteur]
Amand, Séverine [Auteur]
Bailly, Christine [Auteur]
Guilbert, Romain [Auteur]
Hannebique, David [Auteur]
Persoons, Philippe [Auteur]
Arhant, Gwenaëlle [Auteur]
Prévotat, Anne [Auteur]
Reix, Philippe [Auteur]
Hubert, Dominique [Auteur]
Gérardin, Michèle [Auteur]
Chamaillard, Mathias [Auteur]
Prevarskaya, Natalia [Auteur]
Rebuffat, Sylvie [Auteur]
Shapovalov, George [Auteur]
Beekman, Jeffrey [Auteur]
Lejeune, Fabrice [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]

Journal title :

Molecular Therapy

Publisher :

Cell Press

Publication date :

2023-01

ISSN :

1525-0016

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In ...
Show more >Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can correct a nonsense mutation in the Cftr gene in vivo in a new CF mouse model, in utero, and through breastfeeding, thanks, notably, to adequate pharmacokinetic properties. DAP turns out to be very stable in plasma and is distributed throughout the body. The ability of DAP to correct various endogenous UGA nonsense mutations in the CFTR gene and to restore its function in mice, in organoids derived from murine or patient cells, and in cells from patients with cystic fibrosis reveals the potential of such readthrough-stimulating molecules in developing a therapeutic approach. The fact that correction by DAP of certain nonsense mutations reaches a clinically relevant level, as judged from previous studies, makes the use of this compound all the more attractive.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

Submission date :

2024-02-17T03:36:56Z