Author

Jeehye Choi

Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Biology

Supervisor

Dr. Shengwu Ma

Second Advisor

Dr. Norm Huner

Third Advisor

Dr. Susanne Kohalmi, Dr. Anthony Jevnikar

Abstract

Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex-4) are small peptides with potent insulin secretory effect which makes them attractive drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the synthesis of these small peptides is difficult due to recombinant protein degradation and instability.

Human serum transferrin (hTf) is an iron-transport protein that has great potential as an efficient carrier system for protein-based drugs. The use of hTf as a fusion partner will provide a new strategy to enhance the therapeutic potential of GLP-1 and Ex-4. This project investigates the development of transgenic tobacco plants as bioreactors for generating recombinant fusion proteins, GLP-1 - hTf and Ex-4 - hTf. Here, transgenic tobacco plants have successfully accumulated recombinant fusion proteins. Plant-derived proteins showed stability in simulated gastrointestinal environment and confirmed their ability to stimulate insulin secretion from a pancreatic (l-cell line in vitro. Lastly, hTf-fused proteins were shown to internalize into human intestinal epithelial cells in vitro. Collectively, the results suggest that transgenic plants are an effective expression and delivery system of recombinant anti-diabetic proteins.

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