Advantages:
- Novel gene therapy for Type 1 Diabetes (T1D) focused on reprogramming skeletal muscle cells to modulate glucose levels in vivo.
- Nano plasmid DNA of insulin and glucokinase decreased glucose levels in vitro and in vivo and enhanced insulin expression and secretion.
- Groundbreaking treatment for long-lasting blood glucose control without daily injections or lifelong immunosuppression.
Summary:
The study addresses the need for better interventions for Type 1 Diabetes (T1D). Current methods, like daily insulin injections and glucose monitoring, are costly and burdensome. Existing therapies, such as pancreatic beta-cell transplants, require lifelong immunosuppressive drugs, posing risks for patients. This research proposes a new localized in vivo electro gene therapy (liveGT) for T1D to modulate blood glucose in vivo without needing daily insulin injections or immunosuppressive drugs. It aims to deliver insulin and glucokinase genes on one Nano-plasmid DNA directly to glucose transporter 4 expressing cells to reprogram them to modulate blood glucose levels in an insulin-dependent manner.
Our research shows that LiveGT significantly enhanced gene expression and reduced media glucose levels of skeletal muscle cells. In vivo, delivery of LiveGT decreased blood glucose levels compared to untreated rats. LiveGT significantly enhanced human insulin expression and secretion into the bloodstream at physiologically relevant levels for up to 21 days. LiveGT for T1D offers a novel solution in the field as current viral-based gene therapy approaches require immunosuppressive drugs. Non-viral delivery minimizes the risk of immune responses and integration-related complications seen with viral-based therapies. Injections into the muscle is anticipated to last for 6-12 months per injection, which compared to current daily glucose monitoring and insulin injections, would radically improve the lives of T1D patients.
Delivery of reporter gene luciferase to rat skeletal muscle utilizing eight, 150ms, 90V pulses increases gene expression nearly 100- fold across 3-months (A). LiveGT encoding insulin and glucokinase on the same plasmid significantly decreased non-diabetic fed rat blood glucose levels up to seven days compared to untreated controls (B). Human insulin expression and blood circulation at physiological levels (~0.5ulU/mL) was confirmed up to 21 days in rats with liveGT(C).
Desired Partnerships:
- License
- Sponsored Research
- Co-Development