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Characterization of Metabolic Status in Nonhuman Primates with the Intravenous Glucose Tolerance Test
Published on: November 13, 2016
Glucose-responsive probiotics for glycaemic modulation in mice and monkeys
Ningzi Guan1, Deqiang Kong1,2,3, Xianyun Gao1
1Shanghai Key Laboratory of Regulatory Biology, Biomedical Synthetic Biology Research Center, Institute of Biomedical Sciences and School of Life Sciences, Shanghai Academy of Natural Sciences (SANS), East China Normal University, Shanghai, China.
Engineered probiotics deliver glucose-lowering agents orally for diabetes therapy. This living drug senses blood glucose and responds, offering a safe, transplant-free metabolic treatment without external controls.
Area of Science:
- Biotechnology
- Metabolic Engineering
- Microbiome Therapeutics
Background:
- Engineered designer cells offer potential for diabetes therapy through controlled glucose-lowering agent delivery.
- Current methods face safety concerns due to transplantation and reliance on external signal control.
- A need exists for safe, orally deliverable, and responsive therapeutic strategies for diabetes management.
Purpose of the Study:
- To develop an orally deliverable, glucose-sensing probiotic living drug for 'sense-and-respond' blood glucose control.
- To create a synthetic gene circuit for glucose sensing and therapeutic transgene regulation.
- To evaluate the efficacy and safety of this platform in preclinical models of diabetes.
Main Methods:
- Engineered a glucose sensor using the HexR transcriptional regulator and a synthetic promoter.
- Developed oral-deliverable probiotics housing the engineered glucose-sensing gene circuit.
- Administered engineered probiotics orally to diabetic mouse and non-human primate models.
- Assessed glycemic control, lipid profiles, and diabetic complications.
Main Results:
- Demonstrated effective glycemic control in multiple diabetic animal models.
- Showed long-term oral administration improved lipid profiles and attenuated diabetic complications.
- Confirmed the engineered probiotics function as a 'sense-and-respond' therapeutic without transplantation.
Conclusions:
- Engineered probiotics provide a programmable, orally deliverable platform for metabolic therapy.
- This 'living drug' enables real-time, glucose-responsive therapeutic dosing for diabetes.
- The approach offers a safe and effective alternative to transplantation-based cell therapies for diabetes.
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