Sodium voltage-gated channel alpha subunit 9 (SCN9A) pre-messenger RNA (SCN9A pre-mRNA)

SCN9A pre-mRNA is the precursor transcript for the alpha subunit of the voltage-gated sodium channel Nav1.7, a protein that plays a fundamental role in human pain perception. Encoded by the SCN9A gene, this pre-mRNA is primarily expressed in peripheral sensory neurons, such as those in the dorsal root ganglia, where it undergoes splicing to form mature mRNA for Nav1.7 translation. Nav1.7 is essential for the initiation and propagation of action potentials in nociceptors; consequently, genetic variations in SCN9A are directly linked to various pain disorders, including inherited erythromelalgia and congenital insensitivity to pain. Therapeutic targeting of the pre-mRNA using antisense oligonucleotides (ASOs) or RNA interference (RNAi) allows for the selective reduction of Nav1.7 expression, offering a precision medicine approach to treating chronic and neuropathic pain. By modulating the transcript before it is translated, these therapies aim to achieve high isoform specificity, potentially avoiding the cardiovascular and neuromuscular side effects associated with non-selective small-molecule sodium channel blockers. Current clinical development, such as the ASO candidate OLP-1002, focuses on providing long-lasting analgesia for conditions like osteoarthritis by dampening the excitability of the pain-signaling pathway.

Other names

Nav1.7 pre-mRNASCN9A precursor mRNASCN9A transcriptSodium channel protein type 9 subunit alpha pre-mRNA

Splice modulation (exon skipping), RNA interference (RNAi), Antisense-mediated knockdown