Oligonucleotides targeting the 3' splice site downstream of a microexon as an innovative therapy for autism.

ABSTRACT: Microexons are enriched in genes linked to autism spectrum disorders (ASDs). We have previously demonstrated decreased inclusion of a neuronal specific 24 bp microexon of the translational regulator CPEB4 in brains of idiopathic ASD cases and that this leads to CPEB4 aggregation and subsequent under-expression of multiple high confidence ASD-risk genes. Furthermore, decreased inclusion of the CPEB4 microexon is also a novel etiological mechanism in schizophrenia (SCZ). In this work, we designed a series of splice switching antisense oligonucleotides (SSOs) targeting the CPEB4 microexon genomic region. SSOs targeting intronic regions near the microexon resulted in a decrease in microexon inclusion in neuroblastoma cells, by blocking hnRNPC binding, mimicking the isoform

SUBMITTER: Martinez-Pizarro A 

PROVIDER: S-EPMC12628316 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature