Sodium voltage-gated channel alpha subunit 1 messenger RNA (SCN1A mRNA) (SCN1A mRNA)

Sodium voltage-gated channel alpha subunit 1 (SCN1A) messenger RNA is the transcript responsible for the synthesis of the Nav1.1 sodium channel, which is primarily expressed in inhibitory GABAergic interneurons [1, 2]. In conditions like Dravet Syndrome, mutations in one allele of the SCN1A gene lead to haploinsufficiency, resulting in reduced Nav1.1 protein levels and subsequent neuronal hyperexcitability [3, 4]. SCN1A-related RNA has emerged as a therapeutic target through the use of antisense oligonucleotides (ASOs) designed to increase the expression of functional mRNA [1, 2]. For example, the ASO STK-001 targets a naturally occurring non-productive splicing event (poison exon) in the SCN1A pre-mRNA, preventing its inclusion and thereby increasing the pool of productive mRNA available for translation into functional Nav1.1 protein [1, 2]. This approach aims to restore normal sodium channel density and reduce seizure frequency in patients with SCN1A-related epilepsies [1, 4]. Sources: [1] Stoke Therapeutics (2024) Pipeline: STK-001; [2] Lim et al. (2020) Nature Communications 11:3578; [3] UniProt P35498; [4] NIH GARD Dravet Syndrome.

Other names

SCN1A pre-mRNASCN1A transcriptNav1.1 mRNASodium channel protein type 1 subunit alpha RNA

Splice-switching antisense oligonucleotide (ASO) mediated upregulation of functional mRNA levels via Targeted Augmentation of Nuclear Gene Output (TANGO) [1, 2]