Efficient gene delivery to pancreatic islets with ultrasonic microbubble destruction technology

Shuyuan Chen, Jia Huan Ding, Raffi Bekeredjian, Bing Zhi Yang, Ralph V. Shohet, Stephen A. Johnston, Hans E. Hohmeier, Christopher B. Newgard, Paul A. Grayburn

Research output: Contribution to journalArticlepeer-review

173 Scopus citations


This study describes a method of gene delivery to pancreatic islets of adult, living animals by ultrasound targeted microbubble destruction (UTMD). The technique involves incorporation of plasmids into the phospholipid shell of gas-filled microbubbles, which are then infused into rats and destroyed within the pancreatic microcirculation with ultrasound. Specific delivery of genes to islet beta cells by UTMD was achieved by using a plasmid containing a rat insulin 1 promoter (RIP), and reporter gene expression was regulated appropriately by glucose in animals that received a RIP-luciferase plasmid. To demonstrate biological efficacy, we used UTMD to deliver RIP-human insulin and RIP-hexokinase I plasmids to islets of adult rats. Delivery of the former plasmid resulted in clear increases in circulating human C-peptide and decreased blood glucose levels, whereas delivery of the latter plasmid resulted in a clear increase in hexokinase I protein expression in islets, increased insulin levels in blood, and decreased circulating glucose levels. We conclude that UTMD allows relatively noninvasive delivery of genes to pancreatic islets with an efficiency sufficient to modulate beta cell function in adult animals.

Original languageEnglish (US)
Pages (from-to)8469-8474
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number22
StatePublished - May 30 2006
Externally publishedYes


  • Diabetes
  • Gene therapy
  • Ultrasound

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Efficient gene delivery to pancreatic islets with ultrasonic microbubble destruction technology'. Together they form a unique fingerprint.

Cite this