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Gene Therapy Approaches to Promoting Axonal Regeneration After Spinal Cord Injury

Bo, X;Zhang, Y;

Traumatic spinal cord injury is a devastating medical condition that still lacks any effective treatment. Studies on the pathological processes of spinal cord injury and neural repair indicate that the two main obstacles that prevent successful axonal regeneration and functional recovery are the weak intrinsic regenerative capacity of the neurons and the presence of several types of inhibitory molecules in the central nervous system (CNS). Various strategies have been derived and tested to elevate the regenerative status of injured neurons in the CNS or block the inhibitory molecules. Gene therapy approaches have been viewed as the ideal means to treat spinal cord injured patients as they can achieve long-term and localized delivery of therapeutic molecules in the CNS. Ex vivo gene delivery offers the additional advantage of providing cellular support for regenerating axons. In this chapter, we summarize the latest studies on viral vector-mediated gene deliveries in animal models of spinal cord injury. Most of the studies reported so far are aimed at delivery of molecules that pre- vent cell death, or increase intrinsic regenerating state of injured neurons, or modify the CNS environment to make it permissive for axon growth. We also provide detailed protocols used in our lab on gene therapy approaches in promoting axonal regeneration and functional recovery in three animal models.