This workshop interrogates transcript-level engineering using ASOs, including splice-site modulation, exon inclusion/exclusion control, and regulatory element targeting in mutation-driven CNS disease. Rather than reducing transcript levels, these strategies aim to reshape RNA processing, restore functional protein output, or rebalance isoform expression. The session will examine sequence dependency, structural constraints, and translational durability considerations that define success in nondegradative ASO programs.

Highlights Include:

• When is splice modulation superior to transcript knockdown in CNS disease?
• How do steric-block ASOs achieve durable functional rescue without transcript degradation?
• What are the discovery constraints in identifying effective splice-switching sequences?
• Can gain-of-function ASOs reduce dose burden relative to knockdown strategies?