A programmable genetic platform for engineering noninvasive biosensors

Creating genetic sensors for noninvasive visualization of biological activities in optically opaque tissues holds immense potential for basic research and the development of genetic and cell-based therapies. Magnetic resonance imaging (MRI) stands out among deep tissue imaging methods for its ability to generate high-resolution images without ionizing radiation. However, the adoption of MRI as a mainstream biomolecular technology has been hindered by the lack of adaptable methods to link molecular events with genetically encodable contrast. Here, we introduce modular aquaporin-based protease-activatable probes for enhanced reporting (MAPPER), a platform for the systematic creation of genetic sensors for MRI. To develop MAPPER, we engineered protease-activatable MRI reporters using two approaches: protein stabilization and subcellular trafficking. We established the applicability of MAPPER in distinct mammalian cell types and demonstrated its versatility by assembling genetic sensors for diverse targets without requiring extensive customization for each target. MAPPER provides a programmable platform for streamlining the development of noninvasive, nonionizing genetic sensors for biomedical research and in vivo diagnostics.