An electrogenetic interface to program mammalian gene expression by direct current

Huang et al. develop an interface to allow electrode-mediated stimulation of gene expression in human cells, utilizing direct current-generated reactive oxygen species to stimulate transgene expression downstream of the KEAP1-NRF2 biosensor. In a type 1 diabetic mouse model, this interface is demonstrated to ameliorate hyperglycemia by stimulating insulin expression. Wearable electronic devices are playing a rapidly expanding role in the acquisition of individuals' health data for personalized medical interventions; however, wearables cannot yet directly program gene-based therapies because of the lack of a direct electrogenetic interface. Here we provide the missing link by developing an electrogenetic interface that we call direct current (DC)-actuated regulation technology (DART), which enables electrode-mediated, time- and voltage-dependent transgene expression in human cells using DC from batteries. DART utilizes a DC supply to generate non-toxic levels of reactive oxygen species that act via a biosensor to reversibly fine-tune synthetic promoters. In a proof-of-concept study in a type 1 diabetic male mouse model, a once-daily transdermal stimulation of subcutaneously implanted microencapsulated engineered human cells by energized acupuncture needles (4.5 V DC for 10 s) stimulated insulin release and restored normoglycemia. We believe this technology will enable wearable electronic devices to directly program metabolic interventions.

Automated summary

Huang et al. have developed an electrogenetic interface called DART, which allows electrode-mediated stimulation of gene expression in human cells using direct current. In a mouse model of type 1 diabetes, this interface was able to stimulate insulin expression and alleviate hyperglycemia. This technology provides a missing link for wearable electronic devices to directly program gene-based therapies.