Antisense oligonucleotide therapy for patients with Friedreich's ataxia carrying the c.165+5G>C splicing mutation.

ABSTRACT: Friedreich's ataxia (FRDA) is a multisystem, progressive disease. 96% of patients carry biallelic GAA triplet expansion mutations in intron 1 of the frataxin gene (FXN). The remaining 4% have a pathogenic GAA expansion on one FXN allele and another mutation on the second allele. A point mutation, FXN c.165+5G>C, was identified in intron 1 of a patient with FRDA resulting in a significant decrease of FXN levels. Using patient fibroblasts, we demonstrated that the c.165+5G>C mutation affects canonical splicing of FXN, leading to the generation of an aberrant transcript. A library of antisense oligonucleotides (ASOs) was designed to target potential intronic splicing regulator motifs and tested in patient cells. Selected O-methoxyethyl (MOE)-ASOs increased FXN leve

SUBMITTER: Yameogo P 

PROVIDER: S-EPMC12284527 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature