Therapeutic efficacy of lentivirus mediated vasoactive intestinal peptide gene delivery in type 1 diabetes

Objective: Type 1 diabetes (T1DM) is characterized by autoimmune destruction of pancreatic beta cells leading to insulin deficiency. Because vasoactive intestinal peptide (VIP) displayed insulinotropic and anti-inflammatory properties, it has been regarded as a novel therapeutic agent for the treatment of diabetes. Despite all these beneficial properties, VIP is extremely sensitive to peptidases (DPP-4) requiring constant infusions or multiple injections to observe any therapeutic effect. Thus, an HIV-based lentiviral vector encoding human VIP (LentiVIP) was constructed to test the therapeutic efficacy of VIP in multiple-low dose STZ induced animal model of T1DM. Method: 3rd generation of HIV-based lentiviral vectors carrying vasoactive intestinal peptide (LentiVIP) gene was generated to provide a stable VIP gene expression. İn addition, a multi-low dose STZ-induced T1DM experimental animal model was developed to test the potential therapeutic efficacy of LentiVIP. Results: LentiVIP delivery into animal model of T1DM resulted in reduced hyperglycemia, improved glucose tolerance, and prevented weight loss. Decrease in serum CRP levels, and serum oxidant capacity, in addition to improvement in antioxidant capacity were also observed in treated animals. Conclusion: All these beneficial results suggested that LentiVIP delivery should be evaluated as a novel therapeutic approach for the treatment of patients with T1DM. Key words: type 1 diabetes, gene therapy, lentivirus, vasoactive intestinal peptide