biostudies-literatureChacko ANInstitute for Collaborative BiotechnologiesNINDS NIH HHSNational Institutes of HealthChan Zuckerberg InitiativeNIGMS NIH HHSNational Science Foundationeaec1211https://www.ebi.ac.uk/biostudies/studies/S-EPMC12802846biostudies-literatureUnknown12(3)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 apprScience advancesA programmable genetic platform for engineering noninvasive biosensors.PMC128028462024-338493R01 NS128278R35 GM133530W911NF-19-D-0001-00091625770R35-GM1335302308708R01-NS128278Chacko ANPham KXu BTiwari RDhanabalan KMWan JMukherjee AAnderson NTChien RfalseA 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 appr2026-01-01T00:00:00Z2026 Jan2026-06-11T05:22:42.624Z2026-06-11T03:08:24.827ZS-EPMC128028464153378510.1126/sciadv.aec1211