https://science.sciencemag.org/content/365/6460/1469
The study of cellular processes occurring inside intact organisms requires methods to
visualize cellular functions such as gene expression in deep tissues. Ultrasound is a
widely used biomedical technology enabling noninvasive imaging with high spatial and
temporal resolution. However, no genetically encoded molecular reporters are available to
connect ultrasound contrast to gene expression in mammalian cells. To address this
limitation, we introduce mammalian acoustic reporter genes. Starting with a gene cluster
derived from bacteria, we engineered a eukaryotic genetic program whose introduction
into mammalian cells results in the expression of intracellular air-filled protein
nanostructures called gas vesicles, which produce ultrasound contrast. Mammalian
acoustic reporter genes allow cells to be visualized at volumetric densities below 0.5% and
permit high-resolution imaging of gene expression in living animals.