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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., Competing Interests: Declaration of interests J.B. is inventor on a patent related to the FIS assay and received financial royalties from 2017 onward. S.A., C. Bailly, S.R., and F.L. are inventors on a patent demonstrating that DAP is a readthrough molecule useful for the treatment of genetic diseases related to nonsense mutations., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)