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Ultrasound imaging of gene expression in mammalian cells

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Science  27 Sep 2019:
Vol. 365, Issue 6460, pp. 1469-1475
DOI: 10.1126/science.aax4804

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Sounding out mammalian cells

Live cell imaging allows us to observe cellular processes in real time. Most methods rely on light, and the poor penetration of light into tissues limits their application. Ultrasound penetrates tissues, and cellular reporters that respond to ultrasound have been developed recently. These reporters are air-filled protein structures that provide buoyancy in the bacteria they are derived from, but when surrounded by a fluid medium, they reflect sound waves. Farhadi et al. achieved expression from multiple genes to create these complex structures in mammalian cells. In addition to optimizing reporter production and detection, they visualize cells in a proof-of-principle experiment in mouse tumor xenografts.

Science, this issue p. 1469

Abstract

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.

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