An SMN2 splicing-correcting antisense oligonucleotide promotes gene looping and transcription activation.

Targeted histone acetylation at the SMN2 exon 7 region activates the 30-kbp-distant promoter in a human cell line, duplicating the HDAC inhibitor effect.

• Why it matters: Spinal muscular atrophy therapies aim to increase SMN2 exon 7 inclusion, but HDAC inhibitors can have pleiotropic side effects that limit specificity.
• What they did: In a human cell line, a CRISPR-deadCas approach was used to target histone acetylation at the SMN2 E7 region, and chromosome conformation analysis (3C) tested how nusinersen (ASO1) alters chromatin structure.
• The result: ASO1 promotes gene looping in a cohesin-, CTCF-, cleavage/polyadenylation factor-, and canonical poly(A) signal–dependent manner, enabling long-distance promoter activation.

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