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Spatiotemporal control of engineered bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy

Author

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  • Yuhao Chen

    (University of South China
    University of South China
    University of Macau, Taipa)

  • Meng Du

    (University of South China
    University of South China)

  • Zhen Yuan

    (University of Macau, Taipa)

  • Zhiyi Chen

    (University of South China
    University of South China)

  • Fei Yan

    (Chinese Academy of Sciences)

Abstract

Bacteria-based tumor therapy has recently attracted wide attentions due to its unique capability in targeting tumors and preferentially colonizing the core area of the tumor. Various therapeutic genes are also harbored into these engineering bacteria to enhance their anti-tumor efficacy. However, it is difficult to spatiotemporally control the expression of these inserted genes in the tumor site. Here, we engineer an ultrasound-responsive bacterium (URB) which can induce the expression of exogenous genes in an ultrasound-controllable manner. Owing to the advantage of ultrasound in tissue penetration, an acoustic remote control of bacterial gene expression can be realized by designing a temperature-actuated genetic switch. Cytokine interferon-γ (IFN-γ), an important immune regulatory molecule that plays a significant role in tumor immunotherapy, is used to test the system. Our results show that brief hyperthermia induced by focused ultrasound promotes the expression of IFN-γ gene, improving anti-tumor efficacy of URB in vitro and in vivo. Our study provides an alternative strategy for bacteria-mediated tumor immunotherapy.

Suggested Citation

  • Yuhao Chen & Meng Du & Zhen Yuan & Zhiyi Chen & Fei Yan, 2022. "Spatiotemporal control of engineered bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31932-x
    DOI: 10.1038/s41467-022-31932-x
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    1. M. Omar Din & Tal Danino & Arthur Prindle & Matt Skalak & Jangir Selimkhanov & Kaitlin Allen & Ellixis Julio & Eta Atolia & Lev S. Tsimring & Sangeeta N. Bhatia & Jeff Hasty, 2016. "Synchronized cycles of bacterial lysis for in vivo delivery," Nature, Nature, vol. 536(7614), pages 81-85, August.
    2. Di-Wei Zheng & Ying Chen & Zi-Hao Li & Lu Xu & Chu-Xin Li & Bin Li & Jin-Xuan Fan & Si-Xue Cheng & Xian-Zheng Zhang, 2018. "Optically-controlled bacterial metabolite for cancer therapy," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
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    1. Filip Ivanovski & Maja Meško & Tina Lebar & Marko Rupnik & Duško Lainšček & Miha Gradišek & Roman Jerala & Mojca Benčina, 2024. "Ultrasound-mediated spatial and temporal control of engineered cells in vivo," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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