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Swiss scientists unveil ‘gene switch’ patch to start cell therapy for diabetes | The ETH Zurich team states that this cell therapy has the potential to offer a more precise and personalized treatment for diabetes.
Clinically licensed nitroglycerin patches allowed for the on-demand and sustained expression of glucagon-like peptide-1 by human cells engineered with a nitroglycerin-responsive gene switch subcutaneously implanted in mice with type 2 diabetes.
As a proof of concept, we show that percutaneous delivery of NG from clinically licensed dermal patches placed above subcutaneously implanted microencapsulated hNORM-transgenic human cells provides precise, reversible and dynamic NO-triggered control of the expression of the therapeutic protein GLP-1, and can successfully treat experimental type 2 diabetes and obesity in mice over a prolonged period, without affecting parameters such as heart rate and blood pressure. Furthermore, the sGC-inhibitor drug methylene blue 39, 40, clinically licensed for the treatment of methemoglobinemia 41, dose dependently repressed NO-triggered hNORM-mediated transgene expression, thereby providing adjustable dual-drug input control as well as representing a safety switch that could be used to reset hNORM in emergency situations (Fig. For example, the convenient, non-invasive, precise and on-demand trigger delivery from commercially available and Food and Drug Administration (FDA)-approved NG patches is expected to enhance patients’ compliance with treatment and to improve their quality of life, and should ease the path to industrial-scale production of cell-based therapies 75.
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