Related Experiment Video
Updated: May 22, 2025

Neo-Islet Formation in Liver of Diabetic Mice by Helper-dependent Adenoviral Vector-Mediated Gene Transfer
Published on: October 10, 2012
Enhancing GLP-1 expression via IVT mRNA and fusion protein technology for diabetes therapy
Xiaoying Wu1, Jingtao Qiao2, Fei Xiao3
1Peking University Fifth School of Clinical Medicine, Beijing, China; Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Beijing, China.
Background:
Diabetes is a chronic metabolic disorder with high incidence and prevalence worldwide. This study explores a novel glucagon-like peptide-1-Fc (GLP-1-Fc) mRNA designed to improve diabetes management by inducing stable and persistent production of GLP-1-Fc protein.
Methods:
The GLP-1-Fc mRNA was generated using in vitro transcription and fusion protein technology. Protein expression was assessed via western blot and enzyme-linked immunosorbent assay (ELISA) in Human Embryonic Kidney 293T (HEK293T) cells. GLP-1-Fc mRNA and GLP-1-Fc protein (dulaglutide) were administered to C57BL/6J and db/db mice to evaluate protein levels, GLP-1 receptor activity, hypoglycemic effects, and safety using ELISA, lance ultra cAMP assay, blood glucose levels detection, immunofluorescence, and hematoxylin and eosin staining.
Results:
The designed mRNA fused with the Fc region successfully encoded GLP-1-Fc, showing optimal stability and translation efficiency. The GLP-1-Fc protein levels were significantly higher in the GLP-1-Fc mRNA treatment group than those in the control mice. The GLP-1-Fc mRNA effectively reduced blood glucose levels and increased GLP-1 receptor expression in db/db mice after both single and repeated administrations. Moreover, the GLP-1-Fc mRNA provided prolonged glucose reduction with similar efficacy to GLP-1 protein drug, dulaglutide. Besides, intraperitoneal delivery of GLP-1-Fc mRNA does not induce tissue damage.
Conclusions:
Compared to conventional peptide-based therapies, GLP-1-Fc mRNA represents a promising strategy for diabetes treatment by enabling sustained in vivo protein expression, achieving effective glycemic control, and offering a streamlined manufacturing process with reduced production complexity.
More Related Videos
06:21An Ecdysone Receptor-based Singular Gene Switch for Deliberate Expression of Transgene with Robustness, Reversibility, and Negligible Leakiness
Published on: May 7, 2018
11:24Lentiviral Mediated Gene Silencing in Human Pseudoislet Prepared in Low Attachment Plates
Published on: May 14, 2019
Related Concept Videos
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
Dipeptidyl Peptidase 4 Inhibitors
Insulin: Biosynthesis, Chemistry, and Preparation
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
Insulin Secretory Vesicles
Oral Hypoglycemic Agents: Biguanides and Glitazones
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are...