SCN10a-short

SCN10a-short (S10s) is a gene therapy candidate based on a short transcript of the human neuronal sodium channel gene SCN10A, encoding the carboxy-terminal domain. Unlike the full-length SCN10A, which encodes the voltage-gated sodium channel NaV1.8 primarily expressed in neurons, this cardiac-specific isoform is transcribed from an independent promoter and is small enough to be delivered via adeno-associated viral (AAV) vectors[2][3][7]. Overexpression of S10s in cardiomyocytes increases cellular sodium current (INa), maximal action potential upstroke velocity, and action potential amplitude—key factors for proper cardiac conduction[2][7][10]. Preclinical studies show that S10s gene therapy rescues conduction slowing and prevents ventricular tachycardia induced by ischemia-reperfusion injury in animal models and simulated human heart systems[2][7][10]. The mechanism involves modulation of NaV1.5-mediated sodium current through interaction with or regulation of the canonical cardiac sodium channel encoded by SCN5A[3]. This approach aims to treat or prevent life-threatening arrhythmias such as Brugada syndrome and other conduction disorders.

Other names

NaV1.8-shortNaV-1.8-shortNaV 1.8-short