Viral-mediated gene therapy for spinal cord injury (SCI) from a translational neuroanatomical perspective

In this regard, the elongation of injured axons can no longer be deemed a success if the growth is aberrant, and ultimately, non-functional. [...]for the re-establishment of connectivity between growing lesioned axons and neurons, target-directed synaptogenesis is absolutely critical. NTFs are members of a family of endogenously expressed proteins that are abundant during central nervous system (CNS) development and that are essential to promote neuronal survival, synaptogenesis, axon growth and guidance as well as dendritic growth and pruning. Current gene transfer strategies mainly include 1) injections of viral vectors expressing therapeutic transgenes directly into the spinal cord, 2) implantation of cells genetically modified (e.g., fibroblasts, stem cells, etc.) to express particular gene(s) into the cavity created by the lesion and 3) delivery through an intrathecal catheter. Intramuscularly delivered viral vectors are taken up at the neuromuscular junction by the pre-synaptic axon and are retrogradely transported along the peripheral nerves into the corresponding spinal cord motor neurons where the transgenes of interest are expressed.