Sodium channel protein type 9 subunit alpha mRNA (Nav1.7 mRNA)

Sodium channel protein type 9 subunit alpha (Nav1.7) mRNA is the transcript of the SCN9A gene, which encodes a voltage-gated sodium channel essential for pain signaling in the peripheral nervous system [1]. Nav1.7 is primarily expressed in nociceptive neurons within the dorsal root ganglia and trigeminal ganglia, where it acts as a 'threshold channel' that amplifies small depolarizations to trigger action potentials [2]. Genetic studies have identified Nav1.7 as a high-validation target; gain-of-function mutations cause severe pain disorders like erythromelalgia, while loss-of-function mutations result in congenital insensitivity to pain [3]. Targeting the mRNA transcript rather than the protein allows for high isoform selectivity, potentially avoiding the cardiotoxicity associated with inhibiting the closely related Nav1.5 channel [4]. Current therapeutic strategies include antisense oligonucleotides (ASOs) like BIIB115, which are designed to bind the mRNA and trigger its degradation, thereby reducing the density of Nav1.7 channels on the neuronal membrane [5]. This approach aims to provide long-lasting relief for chronic neuropathic pain conditions that are often refractory to conventional analgesics [6]. Sources: [1] UniProt P35498; [2] PubMed PMID: 23505329; [3] Nature Reviews Neurology (2013) 9:526-534; [4] PubMed PMID: 31160518; [5] Biogen R&D Pipeline; [6] Journal of Clinical Investigation (2012) 122(11):3790-3794.

Other names

SCN9A mRNAVoltage-gated sodium channel type IX alpha subunit mRNAPeripheral sodium channel 1 mRNAPN1 mRNANE-NA mRNAEthromelalgia-associated sodium channel mRNA

Antisense oligonucleotide-mediated RNase H degradation of mRNA, RNA interference (siRNA) mediated gene silencing, Splice-switching to induce non-functional isoforms