antisense oligonucleotide targeting DARS2

Antisense oligonucleotide targeting DARS2 is an investigational RNA-targeted therapy designed to treat leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL). LBSL is an ultra-rare neurodevelopmental disorder caused by compound heterozygous mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase. Most patients carry a pathogenic variant in the second intron that disrupts the splicing of exon 3, leading to exon skipping and a nonfunctional protein. The antisense oligonucleotide is designed to target intronic splicing silencers upstream of exon 3, promoting exon 3 inclusion and restoring functional DARS2 protein expression. Preclinical studies in patient-derived induced pluripotent stem cells (iPSCs) and neural progenitor cells (NPCs) have demonstrated that the therapy increases DARS2 exon 3 expression, improves neurite outgrowth, and restores mitochondrial function.

Other names

DARS2 ASODARS-2 ASODARS 2 ASODARS2 antisense oligonucleotideDARS-2 antisense oligonucleotideDARS 2 antisense oligonucleotide