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Review
. 2025 Jun:92:102346.
doi: 10.1016/j.gde.2025.102346. Epub 2025 Apr 9.

No more nonsense: evaluating poison exons as therapeutic targets in neurodevelopmental disorders

Shreeya Bakshi  1 , Lori L Isom  2
Affiliations
Review

No more nonsense: evaluating poison exons as therapeutic targets in neurodevelopmental disorders

Shreeya Bakshi et al. Curr Opin Genet Dev. 2025 Jun.

Abstract

Alternative splicing of pre-mRNA generates multiple transcripts from a single gene, contributing to transcriptomic diversity. Alternative splicing can result in inclusion of poison exons (PEs), which contain a premature stop codons (PTC) that target transcripts for nonsense-mediated decay (NMD). PE-containing transcripts are prevalent in the brain, where they can play roles in fine-tuning mRNA and protein levels. Antisense, or splice-switching, oligonucleotides (ASOs/SSOs) are used to target PEs to reduce their inclusion and treat neurodevelopmental disorders. ASOs/SSOs address the genetic causes of disease and are precision therapies that can provide a cure rather than only address disease symptoms. This review explores the role of PEs in the brain, therapeutic targeting of PEs, and current challenges in our understanding of PEs.

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Conflict of interest statement

Declaration of Competing Interest Lori L. Isom reports financial support was provided by University of Michigan Medical School. Lori L. Isom reports a relationship with University of Michigan Medical School that includes funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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