The dF508 mutation represents the most common cause underlying cystic fibrosis. The resultant misfolding of the nascent cystic fibrosis transmembrane regulator (CFTR) protein and its subsequent proteasomal degradation lead to a deficiency in functional CFTR channels and Cl- efflux at the apical cell membrane in ducts throughout the body (Veit et al. 2016). Small molecule drugs have been identified that rectify this protein misfolding (‘correctors’) and facilitate channel opening (‘potentiators’), thereby restoring CFTR-mediated Cl- efflux at the apical cell membrane and providing clinical improvement (Hanrahan et al. 2017).
Nevertheless, enhanced efficacy remains a key research goal, and evidence indicates that this could be achieved by combining correctors/potentiators with modulators of the ubiquitin proteasomal system (UPS) that regulates CFTR protein degradation (Borgo et al. 2022). There is growing interest in the development of novel treatments that utilise this dual-target approach; we therefore set out to demonstrate that we could:
The presence of sensory neuron markers, excitability properties consistent with sensory neurons, and evidence of nociceptor ion channels (using both RNASeq and electrophysiology) provides strong evidence that iCell Sensory Neurons have a robust sensory neuron phenotype suitable for supporting pain discovery programs.
Using automated patch clamp technology, we evaluate the potency and selectivity of ten Nav1.7-selective arachnid peptide toxins, which have been fused to the C-terminus (Fc region) of human IgG1.