Development of self-delivering RNAi to evaluate PTEN as a therapeutic target to p

Project Summary Innovative drug/therapy combinations directed at multiple and proven therapeutic targets have the potential to dramatically improve outcomes after SCI. Studies on axon regeneration and recovery in rodents have revealed that the spinal cordis not hard wired and learning can occur in spinal cord circuits. Compounds that elicit axonal regeneration and sprouting help plasticity in the spinal cord and dramatically improve recovery from traumatic injury, at least in rodents. Many different compounds/therapies tested in rodents promote regeneration. Almost without exception, compounds that promote regeneration also improve functional recovery after spinal cord injury. Recently, very impressive axon regeneration was obtained from deletion of PTEN.The goal of this application is to simultaneously evaluate PTEN as target for therapeutic treatment of spinal cord injury and a novel RNAi delivery technology to provide prolonged in vivo gene knockdown effect. We will create self-delivering small inte