1.
                        Smart-watch-programmed green-light-operated percutaneous control of therapeutic transgenes.
                        
                        
                        
                        
                            Abstract:
                            Wearable smart electronic devices, such as smart watches, are generally equipped with green-light-emitting diodes, which are used for photoplethysmography to monitor a panoply of physical health parameters. Here, we present a traceless, green-light-operated, smart-watch-controlled mammalian gene switch (Glow Control), composed of an engineered membrane-tethered green-light-sensitive cobalamin-binding domain of Thermus thermophilus (TtCBD) CarH protein in combination with a synthetic cytosolic TtCBD-transactivator fusion protein, which manage translocation of TtCBD-transactivator into the nucleus to trigger expression of transgenes upon illumination. We show that Apple-Watch-programmed percutaneous remote control of implanted Glow-controlled engineered human cells can effectively treat experimental type-2 diabetes by producing and releasing human glucagon-like peptide-1 on demand. Directly interfacing wearable smart electronic devices with therapeutic gene expression will advance next-generation personalized therapies by linking biopharmaceutical interventions to the internet of things.
                        
                        
                    
                
            
                
                    
                        2.
                        Smartphone-controlled optogenetically engineered cells enable semiautomatic glucose homeostasis in diabetic mice.
                        
                        
                            
                                
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                                            Shao, J
                                        
                                    
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                                            Xue, S
                                        
                                    
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                                            Yu, G
                                        
                                    
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                                            Yu, Y
                                        
                                    
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                                            Yang, X
                                        
                                    
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                                            Bai, Y
                                        
                                    
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                                            Zhu, S
                                        
                                    
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                                            Yang, L
                                        
                                    
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                                            Yin, J
                                        
                                    
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                                            Wang, Y
                                        
                                    
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                                            Liao, S
                                        
                                    
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                                            Guo, S
                                        
                                    
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                                            Xie, M
                                        
                                    
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                                            Fussenegger, M
                                        
                                    
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                                            Ye, H
                                        
                                    
 
                        
                        
                            Abstract:
                            With the increasingly dominant role of smartphones in our lives, mobile health care systems integrating advanced point-of-care technologies to manage chronic diseases are gaining attention. Using a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology, we have engineered a technological infrastructure enabling the smartphone-assisted semiautomatic treatment of diabetes in mice. A custom-designed home server SmartController was programmed to process wireless signals, enabling a smartphone to regulate hormone production by optically engineered cells implanted in diabetic mice via a far-red light (FRL)-responsive optogenetic interface. To develop this wireless controller network, we designed and implanted hydrogel capsules carrying both engineered cells and wirelessly powered FRL LEDs (light-emitting diodes). In vivo production of a short variant of human glucagon-like peptide 1 (shGLP-1) or mouse insulin by the engineered cells in the hydrogel could be remotely controlled by smartphone programs or a custom-engineered Bluetooth-active glucometer in a semiautomatic, glucose-dependent manner. By combining electronic device-generated digital signals with optogenetically engineered cells, this study provides a step toward translating cell-based therapies into the clinic.