Electromagnetic wireless remote control of mammalian transgene expression
Zhihua Lin, Preetam Guha Ray, Jinbo Huang, P. Buchmann, Martin Fussenegger
Abstract
Communication between wireless field receivers and biological sensors remains a key constraint in the development of wireless electronic devices for minimally invasive medical monitoring and biomedical applications involving gene and cell therapies. Here we describe a nanoparticle-cell interface that enables electromagnetic programming of wireless expression regulation (EMPOWER) of transgenes via the generation of cellular reactive oxygen species (ROS) at a biosafe level. Multiferroic nanoparticles coated with chitosan to improve biocompatibility generate ROS in the cytoplasm of cells in response to a low-frequency (1-kHz) magnetic field. Overexpressed ROS-responsive KEAP1/NRF2 biosensors detect the generated ROS which is rewired to synthetic ROS-responsive promoters to drive transgene expression. In a proof-of-concept study, subcutaneously implanted alginate-microencapsulated cells stably expressing an EMPOWER-controlled insulin expression system normalized blood-glucose levels in a mouse model of type 1 diabetes in response to a weak magnetic field.