Molecular therapy : the journal of the American Society of Gene Therapy
-
Previous studies have demonstrated that gene transfer of genes coding for neurotrophic factors to the dorsal root ganglion (DRG) using nonreplicating herpes simplex virus (HSV)-based vectors injected subcutaneously can prevent the progression of diabetic neuropathy. Because prolonged expression of neurotrophic factors could potentially have unwanted adverse effects, we constructed a nonreplicating HSV vector, vHrtEPO, to express erythropoietin (EPO) under the control of a tetracycline response element (TRE)-minimal cytomegalovirus (CMV) fusion promoter. ⋯ Mice rendered diabetic by injection of streptozotocin (STZ), inoculated with vHrtEPO, and treated with DOX 4 days out of 7 each week for 4 weeks were protected against the development of diabetic neuropathy as assessed by electrophysiologic and behavioral measures. These studies indicate that intermittent expression of EPO in DRG achieved from a regulatable vector is sufficient to protect against the progression of neuropathy in diabetic animals, and provides proof-of-principle preclinical evidence for the development of such vectors for clinical trial.