Summary There are no approved therapies for spinal cord injury. There are about 300,000 people living with chronic spinal cord injury in US. For the vast majority of them, the injury left them incapable of walking or, if they have suffered a cervical SCI, entirely dependent upon others for assistance in all of their activities of daily living from feeding to personal care. We are developing a neuromodulating gene therapy for treating both acute and chronic SCI patients that will be delivered as a single injection to spinal cord. Neuromodulation after injury has the potential to restore functional recovery, as shown by a number of different investigators. After SCI there is an electrochemical imbalance that prevents motor neurons from eliciting normal muscle actions that are critical for movement of arms and legs. This imbalance is partly caused by a decrease in the chloride transporter called KCC2. It has been shown that by restoring normal levels of this transporter in spared spinal cord neurons, paralyzed mice regain walking ability. Furthermore, enhancement of KCC2 reduces pain and spasticity in rodent models. This grant application aims to examine a new therapy that has the potency and properties to be translated towards human clinical studies, by testing them in preclinical models.