hSCN9A(SD) Rat

The SCN9A gene, which encodes the voltage-gated sodium channel protein Nav1.7, is an important pathogenic factor underlying peripheral neuropathic pain and related rare diseases. Nav1.7 sodium channels mediate the influx of positively charged sodium ions into cells and play a critical role in the generation and propagation of action potentials. Studies have shown that genetic variants in SCN9A are closely associated with multiple inherited pain disorders, including erythromelalgia, small fiber neuropathy, and congenital insensitivity to pain ^[1-2]. As a voltage-gated sodium channel, the Nav1.7 protein is predominantly expressed in sensory and sympathetic neurons of the peripheral nervous system, with particularly high expression in dorsal root ganglia, where it plays an essential role in the generation and transmission of pain signals ^[3]. Research indicates that down-regulation of SCN9A expression or selective inhibition of Nav1.7 holds promise as a novel and highly effective analgesic strategy for the treatment of acute, inflammatory, and neuropathic pain ^[4].

Currently, drug development targeting SCN9A/Nav1.7 continues to advance and encompasses multiple modalities, including small-molecule inhibitors, epigenetic regulation, gene therapy, and biologic agents. Several companies have established relevant pipelines; for example, raxatrigine from GSK has entered Phase III clinical trials for trigeminal neuralgia, while Xenon Pharmaceuticals, Vertex Pharmaceuticals, and others are actively progressing selective Nav1.7 inhibitors in preclinical and early clinical stages ^[5].

hSCN9A(SD) rat is a humanized Scn9a model generated by gene-editing technology. The coding sequence of exon 2 to partial intron 7 of rat Scn9a was replaced with the Kozak-Human SCN9A CDS-3'UTR of Human SCN9A-WPRE-BGH pA cassette. This model can be used for investigating the pathogenic mechanisms of inherited pain disorders such as erythromelalgia, small fiber neuropathy, and congenital insensitivity to pain, as well as for the preclinical research, screening, and evaluation of Nav1.7-targeted analgesic candidates.