Genomically mined acoustic reporter genes for real-time in vivo monitoring of tumors and tumor-homing bacteria

Ultrasound allows imaging at a much greater depth than optical methods, but existing genetically encoded acoustic reporters for in vivo cellular imaging have been limited by poor sensitivity, specificity and in vivo expression. Here we describe two acoustic reporter genes (ARGs)—one for use in bacte...

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Bibliographic Details
Published in:Nature biotechnology 2023-07, Vol.41 (7), p.919-931
Main Authors: Hurt, Robert C., Buss, Marjorie T., Duan, Mengtong, Wong, Katie, You, Mei Yi, Sawyer, Daniel P., Swift, Margaret B., Dutka, Przemysław, Barturen-Larrea, Pierina, Mittelstein, David R., Jin, Zhiyang, Abedi, Mohamad H., Farhadi, Arash, Deshpande, Ramya, Shapiro, Mikhail G.
Format: Article
Language:English
Subjects:
631/1647/245/1859
631/553/552
631/61
Acoustics
Agriculture
Animal tissues
Animals
Archaea
Bacteria
Bacteria - genetics
Bioinformatics
Biological activity
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biopsy
Biotechnology
Breast cancer
Gene clusters
Gene expression
Genes
Genes, Reporter - genetics
Genetic code
Homing
In vivo methods and tests
Life Sciences
Mammalian cells
Mammals
Medical imaging
Mice
Neoplasms - genetics
Neoplasms - therapy
Optics
Phylogeny
Tumors
Ultrasonic imaging
Ultrasound
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Description
Summary:Ultrasound allows imaging at a much greater depth than optical methods, but existing genetically encoded acoustic reporters for in vivo cellular imaging have been limited by poor sensitivity, specificity and in vivo expression. Here we describe two acoustic reporter genes (ARGs)—one for use in bacteria and one for use in mammalian cells—identified through a phylogenetic screen of candidate gas vesicle gene clusters from diverse bacteria and archaea that provide stronger ultrasound contrast, produce non-linear signals distinguishable from background tissue and have stable long-term expression. Compared to their first-generation counterparts, these improved bacterial and mammalian ARGs produce 9-fold and 38-fold stronger non-linear contrast, respectively. Using these new ARGs, we non-invasively imaged in situ tumor colonization and gene expression in tumor-homing therapeutic bacteria, tracked the progression of tumor gene expression and growth in a mouse model of breast cancer, and performed gene-expression-guided needle biopsies of a genetically mosaic tumor, demonstrating non-invasive access to dynamic biological processes at centimeter depth. Gene expression is imaged in deep tissues in mice using ultrasound.
ISSN:1087-0156
1546-1696
DOI:10.1038/s41587-022-01581-y