HSV-mediated gene transfer of C3 transferase inhibits Rho to promote axonal regeneration

Although surgical re-implantation of spinal roots may improve recovery of proximal motor function after cervical root avulsion, recovery of sensory function necessary for fine motor coordination of the hand has been difficult to achieve, in large part because of failure of regeneration of axons into the spinal cord. In order to enhance regeneration, we constructed a non-replicating herpes simplex virus (HSV)-vector carrying the gene coding for bacterial C3 transferase (C3t). Subcutaneous inoculation of the vector into the skin of the forepaw 1 week after a dorsal C5–T1 rhizotomy resulted in expression of C3t in dorsal root ganglion (DRG) neurons and inhibition of Rho GTPase activity, resulting in extensive axonal regeneration into the spinal cord that correlated with improved sensory-motor coordination of the forepaw.

► An HSV vector expressing C3 transferase (vC3t) inhibits Rho GTPase activity.
► Transfection with vC3t enhances axonal regeneration after cervical rhizotomy.
► Axonal regeneration was accompanied by improved behavioral recovery.