Ser-TASK3-siRNA

Ser-TASK3-siRNA is a **conjugated small interfering RNA (siRNA) therapeutic** specifically designed to knockdown the TASK3 potassium channel (KCNK9) in serotonin (5-HT) neurons. It is created by conjugating TASK3-targeting siRNA with **sertraline** (Ser), a ligand that targets the serotonin transporter, enabling selective accumulation and uptake in monoamine (serotonergic) neurons after **intranasal administration**. Once delivered, the siRNA is internalized, directing RNA-induced silencing complex (RISC) machinery to degrade TASK3 mRNA, thereby **reducing TASK3 channel expression and function**. In preclinical mouse models, this selective knockdown demonstrated **robust antidepressant-like effects, enhanced hippocampal plasticity, and potentiation of SSRI action**, indicating potential as a novel, neuron-targeted antidepressant strategy[1].