2016 Pathway Accelerator Awardee Zhen Gu, PhD

Engineering an automated insulin-delivery system

Project title: Bio-Inspired Synthetic Pathway for Closed-Loop Delivery of Insulin and Glucagon
Institution: North Carolina State University and University of North Carolina at Chapel Hill
Pathway project publications: 5
Has filed 4 pathway project-related patents to date

Major accomplishments:

We have developed a transformative glucose-responsive insulin delivery device using a microneedle-array patch ("smart insulin patch") containing insulin vesicles that dissociate and rapidly release insulin in the hyperglycemic environment. This device effectively regulated the blood glucose in a mouse model of type 1 diabetes. The faster responsiveness of this approach holds promise in avoiding hyperglycemia and hypoglycemia if translated to human disease. The relevant studies have been published by PNAS (2015) and ACS Nano (2017).

We have further developed an innovative microneedle (MN)-based cell therapy, which could achieve glucose-responsive regulation of the insulin secretion from exogenous pancreatic β-cells without implantation. One MN patch could quickly reduce blood sugar levels of chemically-induced type 1 diabetic mice and stabilize BGLs at a reduced level for over 10 hours. The relevant study has been published by Advanced Materials (2016).

Very recently, we have also reported the development of a new glucose-responsive insulin delivery system based on the interaction between the glucose derivative-modified insulin and glucose transporters on red blood cells (RBCs) membrane. After being conjugated with the glucosamine, insulin can efficiently bind to RBC membranes. The binding is reversible in the setting of hyperglycemia, resulting in fast release of insulin and subsequent drop of blood glucose level in vivo. The relevant study has been published by Advanced Materials (2017).

Impact statement:

Current standard care for type 1 and advanced type 2 diabetes requires consistent monitoring of blood glucose levels and subsequent insulin injections. An artificial pancreas that continuously releases insulin in response to blood glucose level changes offers to improve the quality of life for people with diabetes. Automated closed-loop insulin delivery devices have integrated a continuous glucose monitoring sensor with an external insulin infusion pump. Obstacles, such as guaranteeing accurate feedback and preventing failures in insulin infusion, still persist today. Our approach uses artificial vesicles, mimicking the function of vesicles inside pancreatic cells for "secreting" insulin or glucagon at the right time. Our research is highly innovative and successful implementation will accelerate development of the next-generation artificial pancreases. When successfully demonstrated, this research will be rapidly tested in human studies.

This Pathway award has already significantly promoted my career development. I can concentrate on the emerging research field without funding pressure; I can carry out high-risk/high-gain projects in an efficient way. To date, with Pathway's support, we have already published several research papers in high-impact journals. Our research has been highlighted by Science, Nature, the Washington Post, the Boston Globe and MIT Technology Reviews. More importantly, we have already launched a startup company (Zenomics), aiming to translate our "smart insulin" technology, directly generated by the terrific support of this Pathway award.