4.8 Article

Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation

Journal

SMALL
Volume 17, Issue 31, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202008177

Keywords

cell metabolism; diabetes; gene transfection; microbubbles; ultrasound

Funding

  1. National Key RAMP
  2. D Program of China [2018YFC0115900]
  3. National Natural Science Foundation of China [82030048, 81527803, 81901871, 82001818]
  4. Zhejiang Science and Technology Project [2019C03077, Y16H180019]
  5. Natural Science Foundation of Zhejiang Province [Y16H180019, LQ21H180007]
  6. Natural Science Foundation of Guangdong Province [2016A030311054]
  7. Shanghai Rising-Star Program [19QA1404800]
  8. Innovation Research Plan by the Shanghai Municipal Education Commission [ZXWF082101]
  9. Second Affiliated Hospital of Zhejiang University [2019002]

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The study demonstrated successful gene delivery of GLP-1 in macaques using UTMD, leading to enhanced GLP-1 expression and improvement in pancreatic beta cell regeneration and plasma glucose regulation. This approach shows promising alternatives for treating type 2 diabetes.
Ultrasound-targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon-like peptide 1 (GLP-1) in ultrasound-induced microbubbles, toward treatment of T2D in macaque. The as designed UTMD afforded enhancement of cell membrane penetration and GLP-1 expression in macaque, which is characterized by ultrasound-guided biopsy to monitor the dynamic process of islet cells for 6 months. Also, improvement of pancreatic beta cell regeneration, and regulation of plasma glucose in macaque with T2D is achieved. The approach would serve as promising alternatives for the treatment of T2D.

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