Development of an exon 27-skipping antisense oligonucleotide as a targeted therapy for refractory skin ulcers in Werner syndrome.

Antisense oligonucleotide (WRN-108) inducing exon 27 skipping to restore the *WRN* reading frame

This study develops WRN-108, a splice-switching antisense oligonucleotide (ASO) inducing exon 27 skipping to restore the WRN reading frame in patients carrying the most common Japanese founder mutation. Werner syndrome causes refractory skin ulcers. WRN-108 restores a truncated but partially functional WRN protein with demonstrated benefits in vitro and ex vivo on keratinocytes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Werner syndrome illustrates the ASO approach for genodermatoses with population-specific recurrent mutations. The ex vivo keratinocyte data is a concrete step toward a clinical trial, though generalization to other WRN mutations will remain a challenge.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 7/10