Personalized allele-specific antisense oligonucleotides for GNAO1-neurodevelopmental disorder.

ABSTRACT: GNAO1-associated disorders are ultra-rare autosomal dominant conditions, which can manifest, depending on the exact pathogenic variant in GNAO1, as a spectrum of neurological phenotypes, including epileptic encephalopathy, developmental delay with movement disorders, or late-onset dystonia. There are currently no effective treatments available, apart from symptomatic options. In this work, we suggest harnessing personalized RNA therapy to treat GNAO1 patients and focus specifically on a recurrent pathogenic variant (E246K). We systemically screened allele-specific antisense oligonucleotides (ASOs) targeting the mutated allele to identify a potent and specific sequence using both reporter-based platforms and a patient-derived cellular model. We show that reduction of mutated <

SUBMITTER: Shomer I 

PROVIDER: S-EPMC11787015 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature