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By screening natural prokaryotic gas vesicle gene clusters, we found and engineered new acoustic reporter genes (ARGs) that give bacteria and mammalian cells brighter ultrasound contrast for real-time noninvasive imaging. Expressing these ARGs in engineered cells enabled us to image tumor-homing bacteria and perform genetically guided tumor biopsies in vivo.
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References
Piraner, D. I. et al. Going deeper: biomolecular tools for acoustic and magnetic imaging and control of cellular function. Biochemistry 56, 5202–5209 (2017). This review article discusses the challenges of using optical methods to image cells in living tissues and presents acoustic and magnetic methods as alternatives with deeper tissue penetration depth.
Bourdeau, R. W. et al. Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts. Nature 553, 86–90 (2018). This paper reports the first-generation bacterial acoustic reporter genes that enabled visualization of bacteria in live animals using ultrasound but were limited because they could not be expressed in situ.
Farhadi, A. et al. Ultrasound imaging of gene expression in mammalian cells. Science 365, 1469–1475 (2019). This paper reports the first-generation mammalian acoustic reporter genes that enabled visualization of mammalian cells in live animals using ultrasound but were limited because they required destructive imaging.
Maresca, D. et al. Nonlinear X-wave ultrasound imaging of acoustic biomolecules. Phys. Rev. X 8, 041002 (2018). This paper reports an amplitude-modulation pulse sequence that enables nonlinear, nondestructive ultrasound imaging of gas vesicles.
Lakshmanan, A. et al. Acoustic biosensors for ultrasound imaging of enzyme activity. Nat. Chem. Biol. 16, 988–996 (2020). This paper reports a use of GVs as genetically encodable intracellular biosensors for enzymatic activity.
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This is a summary of: Hurt, R. C. et al. Genomically mined acoustic reporter genes for real time in vivo monitoring of tumors and tumor-homing bacteria. Nat. Biotechnol. https://doi.org/10.1038/s41587-022-01581-y (2023).
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Real-time monitoring of tumor-homing bacteria and tumor cells in vivo using ultrasound.
Nat Biotechnol (2023). https://doi.org/10.1038/s41587-022-01590-x
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DOI: https://doi.org/10.1038/s41587-022-01590-x
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Erasmo Ramage