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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月10日

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  • 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,
  • Huixiong Xu

摘要

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.