Promoting readthrough of nonsense mutations in CF mouse model: Biodistribution and efficacy of NV848 in rescuing CFTR protein expression.

ABSTRACT: Nonsense mutations, often resulting from single-nucleotide substitutions, produce mRNA harboring a premature termination codon (PTC), which causes the premature termination of protein synthesis. This produces truncated and non-functional proteins, which cause different genetic diseases, including cystic fibrosis (CF). This work aims to investigate the ability of NV848 (N-(5-methyl-1,2,4-oxadiazol-3-yl)acetamide), a translational readthrough-inducing drug (TRID), to rescue CF transmembrane conductance regulator (CFTR) protein expression in a murine model characterized by the G542X nonsense mutation in the CFTR gene. In vitro experiments assessed the drug's stability in human hepatic metabolism, and in vivo investigations on wild-type mice allowed us to clarify the distribution of the drug t

SUBMITTER: Fiduccia I 

PROVIDER: S-EPMC11638873 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature