Targeting rare splicing defects: Antisense oligonucleotides offer a therapeutic strategy in FRDA

Targeting rare splicing defects: Antisense oligonucleotides offer a therapeutic strategy in FRDA, Kerkhof, Laurie M.C. et al., Molecular Therapy Nucleic Acids, Volume 36, Issue 4, 102723 doi:10.1016/j.omtn.2025.102723

Using patient-derived cells, the authors demonstrated that antisense oligonucleotides (ASOs) targeting splicing regulatory elements effectively restore splicing deficits and increase frataxin expression. While encouraging in cell-based studies, this strategy is limited to a small subset of individuals with FRDA carrying these rare mutations and requires functional validation in disease-relevant tissues.