ID: 2175

• Title:
  Gene Electrotransfer Mediated Insulin and Glucokinase Delivery Modulates Glucose
  
  Authors:
  

  Hensley, Jacob - Department of Chemistry, University of South Florida, Tampa, FL, USA
  Kailes, Benjamin - Department of Chemistry, University of South Florida, Tampa, FL, USA
  Francis, Michael - Asante Bio, Tampa, FL, USA
  Otten, Alex - Department of Electrical Engineering, University of South Florida, Tampa, FL, USA
  Bulysheva, Anna - Department of Medical Engineering, University of South Florida, Tampa, FL, USA

  
  
  Abstract:
  More than 9 million adults are diagnosed with Type 1 Diabetes (T1D) worldwide. Traditional therapies utilize insulin protein injections and continuous glucose monitoring. Islet cell and stem cell transplants are more recent clinical therapeutic advancements; however, they require immunomodulation. Insulin and glucokinase delivery via AAV show promising results, although immunomodulation is still required due to the viral delivery vehicle. The goal of this study is to deliver insulin and glucokinase via gene electrotransfer (GET) for glucose modulation. Transient transfection of myoblasts via GET with Nanoplasmid ® DNA encoding insulin and glucokinase was examined to overcome the need for immunomodulatory drugs. Following transfection, media glucose levels were measured daily for three days. One-way ANOVA comparison and Tukey multiple comparison tests were used for quantitative statistical analysis. Immunofluorescence analysis measured transfection efficiency. Exogenous co-expression of both insulin and glucokinase significantly reduced media glucose levels compared to respective controls, indicating that GET delivery of insulin and glucokinase is a viable therapeutic pathway. Myoblast cells that express glucose transporter-4 modulate glucose in an insulin dependent manner. These observations are consistent with our hypothesis that skeletal muscle cells can be reprogrammed to modulate blood glucose levels, resulting in a potential treatment for type 1 diabetes without the use of immunomodulatory drugs.
  
  
  
  
  
  Keywords:
  Insulin, Diabetes, Gene Electrotransfer, Glucose
  
  Refs:
  
  
  Topic 1:
  1. Biological responses (molecular, subcellular, cellular and intercellular)
  
  Topic 2:
  13. Pulsed power devices and methods