SCN1A natural antisense transcript (SCN1ANAT) (SCN1ANAT)

The SCN1A natural antisense transcript (SCN1ANAT, also known as AC010127.3) is a non-coding RNA that overlaps and negatively regulates the SCN1A gene, which encodes the Nav1.1 voltage-gated sodium channel alpha subunit essential for neuronal excitability. By forming RNA-RNA interactions or influencing chromatin, SCN1ANAT suppresses SCN1A expression, contributing to reduced Nav1.1 protein levels in conditions like Dravet syndrome, a severe developmental epileptic encephalopathy caused by SCN1A loss-of-function mutations. In Dravet syndrome, depleting or blocking SCN1ANAT with antisense oligonucleotides (ASOs) or AntagoNATs upregulates canonical SCN1A transcripts, increases functional Nav1.1, and ameliorates disease phenotypes in patient-derived neurons and mouse models. This approach shows allele-specific potential and is advancing to clinical testing. Therapeutic challenges include ensuring specificity to avoid disrupting normal developmental regulation of SCN1A poison exons, which are sensitive to nonsense-mediated decay (NMD).

Other names

AC010127.3

Upregulation of SCN1A expression by inhibiting the antisense transcript, Splice modulation to reduce poison exon inclusion in SCN1A