A therapeutic antisense oligonucleotide encompassing 2'-<i>O</i>-methoxyethyl modification triggers unique perturbation of the transcriptome.

ABSTRACT: Nusinersen, an antisense oligonucleotide (ASO) encompassing a phosphorothioate backbone and 2'-O-methoxyethyl (MOE) modifications, is commonly used for the treatment of spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. Nusinersen acts through prevention of skipping of exon 7 of Survival Motor Neuron 2 (SMN2) by sequestering Intronic Splicing Silencer N1 (ISS-N1), located within SMN2 intron 7. Here, we report transcriptome-wide perturbations triggered by ISS-N1-targeting ASOs incorporating diverse modifications, including F18MOE, an 18mer ASO with identical sequence and chemical composition to that of nusinersen. Among cellular processes most impacted by F18MOE were cell cycle, cell growth, cell signaling, and maintenance of the cytosk

SUBMITTER: Ottesen EW 

PROVIDER: S-EPMC12805893 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature