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Multiplexed Ultrasound Imaging of Gene Expression
Open accessPreprint — published as 10.1038/s41592-025-02825-w
Abstract
Acoustic reporter genes (ARGs) have enabled the imaging of gene expression with ultrasound, which provides high-resolution access to deep, optically opaque living tissues. However, unlike their fluorescent counterparts, ARGs have so far been limited to a single “color,” preventing multiplexed imaging of cellular states or populations. Here, we use rational protein design and directed evolution to develop two novel ARGs that can be distinguished from each other based on their acoustic pressure response profiles, enabling “two-color” ultrasound imaging of gene expression. We demonstrate the utility of multiplexed ARGs for delineating bacterial cell species and cell states in vitro , and then apply them towards imaging distinct subpopulations of probiotics in the mouse gastrointestinal tract and in tumor-colonizing bacterial agents in vivo . Just as the first wavelength-shifted derivatives of fluorescent proteins opened a vivid world for optical microscopy, our next-generation acoustic proteins set the stage for a richer symphony of ultrasound signals from living subjects.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Metadata
- Authors
- Nyström, N. N., Jin, Z., Bennett, M. E., Zhang, R., Swift, M. B., & Shapiro, M. G.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Shapiro, Mikhail G.
- Venue
- Nature Methods
- Publisher
- openRxiv
- Published
- 2024-11-03
- Volume
- 22
- Issue
- 12
- Pages
- 2594-2600
- ISSN
- 1548-7091 (ISSN-L)
- PMC
- PMC12695634
- OpenAlex
- W4416337525
- Cited by
- 5
- References
- 1
- Citations by year
- 2026: 4 · 2025: 1
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Methods (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- U.S. Department of Health and Human Services
- Life Sciences Research Foundation
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (R01EB018975)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Physical Sciences › Engineering › Biomedical Engineering › Photoacoustic and Ultrasonic Imaging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › bioluminescence and chemiluminescence research
- Keywords
- multiplexed imaging, rational protein design, directed evolution, gastrointestinal tract
- MeSH terms
- Animals, Humans, Ultrasonography, Gene Expression, Genes, Reporter, Gastrointestinal Tract, Mice
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