Proteins, air and water: reporter genes for ultrasound and magnetic resonance imaging

A long-standing goal of molecular imaging is to visualize cellular function within the context of living animals, necessitating the development of reporter genes compatible with deeply penetrant imaging modalities such as ultrasound and magnetic resonance imaging (MRI). Until recently, no reporter genes for ultrasound were available, and most genetically encoded reporters for MRI were limited by metal availability or relatively low sensitivity. Here we review how these limitations are being addressed by recently introduced reporter genes based on air-filled and water-transporting biomolecules. We focus on gas-filled protein nanostructures adapted from buoyant microbes, which scatter sound waves, perturb magnetic fields and interact with hyperpolarized nuclei, as well as transmembrane water channels that alter the effective diffusivity of water in tissue. ; © 2018 Elsevier Ltd. Available online 14 March 2018. We thank members of the Shapiro Laboratory for helpful discussions. Related work in the Shapiro laboratory is also supported by the Heritage Medical Research Institute, the National Institutes of Health, the Defense Advanced Research Projects Agency, the Jacobs Institute for Molecular Engineering in Medicine, the Caltech Center for Environmental Microbial Interactions, the Human Frontiers Science Program, the Burroughs Wellcome Fund, the Pew Scholarship in the Biomedical Sciences, the Sontag Foundation, the Packard Fellowship for Science and Engineering. A.F. is supported by the Natural Sciences and Engineering Research Council of Canada PGSD. Author contributions: All authors wrote the manuscript. The authors declare no competing financial interests. ; Accepted Version - nihms951463.pdf