Modulation of DNA transcription: The future of ASO therapeutics?

Abstract

In this issue of Cell, Kornblihtt and colleagues report a strategy to improve antisense oligonucleotide spinal muscular atrophy therapy. They discover that the oligonucleotide drug nusinersen, which induces exon inclusion, also promotes repressive chromatin modifications, which in turn work against exon inclusion. Notably, co-administration of histone deacetylase inhibitors counteracted this effect to augment exon inclusion.