BLOC1S1-targeting splice-switching oligonucleotides

BLOC1S1-targeting splice-switching oligonucleotides are antisense oligonucleotides (ASOs) designed to treat amyotrophic lateral sclerosis (ALS) by reducing the expression of BLOC1S1 (also known as GCN5L1). The lead candidate, SSO 1628, is a 2'-MOE modified phosphorothioate oligonucleotide that targets exon 2 of the BLOC1S1 pre-mRNA, inducing exon skipping and subsequent transcript degradation via nonsense-mediated decay (NMD). BLOC1S1 is a regulator of mitochondrial acetylation that is upregulated in ALS; its depletion aims to reverse mitochondrial hyper-acetylation and improve mitochondrial respiration. Developed by researchers at A*STAR in Singapore, these SSOs have demonstrated the ability to rescue disease phenotypes in patient-derived motor neurons and extend survival in ALS mouse models.

Other names

BLOC1S1 SSOsBLOC-1S1 SSOsBLOC 1S1 SSOsGCN5L1-targeting splice-switching oligonucleotidesGCN-5L1-targeting splice-switching oligonucleotidesGCN 5L1-targeting splice-switching oligonucleotides