Abstract
bioRxiv [Preprint]. 2025 Nov 30:2025.11.26.690143. doi: 10.1101/2025.11.26.690143.
ABSTRACT
TDP-43 nuclear depletion in amyotrophic lateral sclerosis (ALS) causes de-repression of cryptic exons (CEs) in multiple transcripts, including UNC13A and STMN2, disrupting synaptic transmission and neurite outgrowth. We developed a therapeutic U7 snRNA (tU7) approach that suppresses TDP-43-dependent mis-splicing, restores target gene expression, rescues neuronal functions in human iPSC-derived neurons, and shows target engagement in vivo, positioning tU7-mediated splicing correction as a promising therapeutic strategy for ALS.
PMID:41394711 | PMC:PMC12697360 | DOI:10.1101/2025.11.26.690143
UK DRI Authors
