Sodium channel protein type 1 subunit alpha (SCN1A) mRNA (SCN1A mRNA)

SCN1A mRNA encodes the alpha subunit of the voltage-gated sodium channel Nav1.1, which is primarily expressed in GABAergic inhibitory interneurons and is essential for maintaining the balance of excitation and inhibition in the central nervous system (UniProt P35498). Mutations in the SCN1A gene, typically resulting in haploinsufficiency, are the primary cause of Dravet syndrome, a severe, treatment-resistant form of childhood-onset epilepsy (NCBI Gene ID 6323). SCN1A mRNA has become a focal point for precision medicine, specifically through the use of antisense oligonucleotides (ASOs) designed to increase the expression of functional mRNA from the non-mutated allele. For example, the drug candidate STK-001 utilizes Targeted Augmentation of Nuclear Gene Output (TANGO) technology to bind to SCN1A pre-mRNA, preventing non-productive splicing and thereby increasing the levels of mature, productive mRNA (Stoke Therapeutics; Lim et al., 2020, Nature Communications). This approach aims to restore Nav1.1 protein levels to physiological norms, potentially addressing the underlying cause of seizures and cognitive impairment in affected patients. Unlike traditional anti-seizure medications that provide symptomatic relief, targeting SCN1A mRNA offers a disease-modifying strategy by directly modulating the genetic output of the cell. Clinical trials are currently evaluating the safety and efficacy of these mRNA-modulating therapies in pediatric populations (ClinicalTrials.gov).

Other names

Nav1.1 mRNASCN1A transcriptSodium channel voltage-gated type I alpha subunit mRNANAC1 mRNAFEB3 mRNAEIEE6 mRNA

Targeted Augmentation of Nuclear Gene Output (TANGO) using antisense oligonucleotides to modulate splicing and increase productive mRNA levels (Lim et al., 2020, Nature Communications).