Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation.
Paul A. Grayburn M.D.
Zhang, C., Chen, S., Li, Q., Wu, J., Qiu, F., Chen, Z., Sun, Y., Luo, J., Bastarrachea, R.A., Grayburn, P.A., DeFronzo, R.A., Liu, Y., Qian, K. and Huang, P. (2021). “Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation.” Small Jun 29;e2008177. [Epub ahead of print]. e2008177.
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.