Jiawei Shao

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.

Electronic control of designer cells There is increasing interest in using designer cells to produce or deliver therapeutics. Achieving direct communication between such cells and electronic devices would allow precise control of therapies. Krawczyk et al. describe a bioelectronic interface that uses wireless-powered electrical stimulation of cells to promote the release of insulin (see the Perspective by Brier and Dordick). The authors engineered human β cells to respond to membrane depolarization by rapidly releasing insulin from intracellular storage vesicles. A bioelectronic device that incorporates the cells can be wirelessly triggered by an external field generator. When subcutaneously implanted in type 1 diabetic mice, the device could be triggered to restore normal blood glucose levels. Science , this issue p. 993 ; see also p. 936

Significance We have developed an optogenetic far-red light (FRL)-activated CRISPR-dCas9 system (FACE) that is orthogonal, fine-tunable, reversible, and has robust endogenous gene-activation profiles upon stimulation with FRL, with deep tissue penetration capacity, low brightness, short illumination time, and negligible phototoxicity. The FACE device is biocompatible and meets the criteria for safe medical application in humans, providing a robust differentiation strategy for mass production of functional neural cells from induced pluripotent stem cells simply by utilizing a beam of FRL. This optogenetic device has expanded the optogenetic toolkit for precise mammalian genome engineering in many areas of basic and translational research that require precise spatiotemporal control of cellular behavior, which may in turn boost the clinical progress of optogenetics-based precision therapy.

oncogene in a mouse xenograft tumor model. Beyond extending the spectrum of light energies in optogenetic toolbox for CRISPR-Cas9 technologies, this study demonstrates how FAST system can be deployed for programmable deep tissue gene editing in both biological and biomedical contexts toward high precision and spatial specificity.