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Ultrasound Imaging of Gene Expression in Mammalian Cells

View ORCID ProfileArash Farhadi, View ORCID ProfileGabrielle H. Ho, View ORCID ProfileDaniel P. Sawyer, View ORCID ProfileRaymond W. Bourdeau, View ORCID ProfileMikhail G. Shapiro
doi: https://doi.org/10.1101/580647
Arash Farhadi
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA.
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Gabrielle H. Ho
2Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA.
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Daniel P. Sawyer
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA.
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Raymond W. Bourdeau
2Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA.
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Mikhail G. Shapiro
2Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA.
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  • ORCID record for Mikhail G. Shapiro
  • For correspondence: mikhail@caltech.edu
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ABSTRACT

The study of cellular processes occurring inside intact organisms and the development of cell-based diagnostic and therapeutic agents requires methods to visualize cellular functions such as gene expression in deep tissues. Ultrasound is a widely used biomedical technology enabling deep-tissue 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 the first mammalian acoustic reporter genes. Starting with an eleven-gene polycistronic gene cluster derived from bacteria, we engineered a eukaryotic genetic program whose introduction into mammalian cells results in the expression of a unique class of intracellular air-filled protein nanostructures called gas vesicles. The scattering of ultrasound by these nanostructures allows mammalian cells to be visualized at volumetric densities below 0.5%, enables the monitoring of dynamic circuit-driven gene expression, and permits high-resolution imaging of gene expression in living animals. These mammalian acoustic reporter genes enable previously impossible approaches to monitoring the location, viability and function of mammalian cells in vivo.

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Posted March 18, 2019.
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Ultrasound Imaging of Gene Expression in Mammalian Cells
Arash Farhadi, Gabrielle H. Ho, Daniel P. Sawyer, Raymond W. Bourdeau, Mikhail G. Shapiro
bioRxiv 580647; doi: https://doi.org/10.1101/580647
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Ultrasound Imaging of Gene Expression in Mammalian Cells
Arash Farhadi, Gabrielle H. Ho, Daniel P. Sawyer, Raymond W. Bourdeau, Mikhail G. Shapiro
bioRxiv 580647; doi: https://doi.org/10.1101/580647

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