Self-delivering RNAi to promote axon regeneration

DESCRIPTION (provided by applicant): After neurotrauma, neurons in the central nervous system (CNS) do not regenerate their injured axons. Intrinsic signals that progress with normal neuronal differentiation play a significant role in preventing axon regeneration. Several intrinsic negative regulators of regeneration have been identified through studies of knock-out mice. We will design and test novel self-deliverable RNA interference (sdRNAi) compounds as an approach to evaluate intrinsic barriers to regeneration as therapeutic targets. We will use novel sdRNAi technology, which does not require any additional delivery formulation, to reduce the risk of inflammation and non-specific effects, which are of special concern with RNAi injected into the CNS. sdRNA has been proven effective in vivo without the need for special delivery packaging or liposomes. For clinical development, it will be important to determine if sdRNA against intrinsic regulators needs to be injected in the vicinity of the cell body,