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Transdermal microneedle-assisted ultrasound-enhanced CRISPRa system to enable sono-gene therapy for obesity

Author

Listed:
  • Shaoyue Li

    (Tongji University
    Fudan University
    Tongji University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Jifeng Yu

    (Fudan University)

  • Yuting Shen

    (Fudan University)

  • Bing Xiong

    (Fudan University)

  • De Zhao

    (Tongji University
    Tongji University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Weichen Xu

    (Tongji University
    Tongji University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Shen Zhang

    (Tongji University
    Fudan University
    Tongji University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Xin Guan

    (Fudan University)

  • Yunyun Liu

    (Tongji University
    Fudan University
    Tongji University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Xuexia Shan

    (Tongji University
    Tongji University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Anqi Zhu

    (Fudan University)

  • Qi Lyu

    (Fudan University)

  • Yan Fang

    (Fudan University)

  • Zitong Chen

    (Fudan University)

  • Haohao Yin

    (Fudan University)

  • Liping Sun

    (Tongji University
    Tongji University
    Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment)

  • Huixiong Xu

    (Fudan University)

Abstract

Obesity, a surging global health challenge, necessitates effective, accessible and innovative therapeutic models. Here we develop a spatiotemporally controllable microneedle (MN) drug delivery platform for sono-gene therapy to fight obesity. The platform delivers the methoxy polyethylene glycol-polyethyleneimine (mPEG-PEI) modified metal-organic frameworks (MOFs) sonosensitizer and the clustered regularly interspaced short palindromic repeats-activating (CRISPRa)/CRISPRa-uncoupling protein 1 (UCP1) system intradermally to adipocytes. Overall, this therapy platform is capable of achieving two major strategies of “annihilation” and “countermeasure”: one is to kill redundant white adipocytes by sonodynamic therapy, and the other is to promote the browning of white adipocytes through the controllable release of CRISPRa-UCP1 system and sonodynamic effect. Obese male mice treated with this sono-gene therapy shows significant ameliorate in glucose tolerance and insulin sensitivity, successfully achieves weight loss and restrains weight rebound. This study may enable a standard treatment paradigm for sono-gene therapy of obesity and other metabolic diseases.

Suggested Citation

  • Shaoyue Li & Jifeng Yu & Yuting Shen & Bing Xiong & De Zhao & Weichen Xu & Shen Zhang & Xin Guan & Yunyun Liu & Xuexia Shan & Anqi Zhu & Qi Lyu & Yan Fang & Zitong Chen & Haohao Yin & Liping Sun & Hui, 2025. "Transdermal microneedle-assisted ultrasound-enhanced CRISPRa system to enable sono-gene therapy for obesity," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56755-4
    DOI: 10.1038/s41467-025-56755-4
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    References listed on IDEAS

    as
    1. Edward T. Chouchani & Lawrence Kazak & Mark P. Jedrychowski & Gina Z. Lu & Brian K. Erickson & John Szpyt & Kerry A. Pierce & Dina Laznik-Bogoslavski & Ramalingam Vetrivelan & Clary B. Clish & Alan J., 2016. "Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1," Nature, Nature, vol. 532(7597), pages 112-116, April.
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