Ultrasound-Targeted Microbubble Destruction Can Repeatedly Direct Highly Specific Plasmid Expression to the Heart
作者:
Raffi Bekeredjian,
Shuyuan Chen,
Peter Frenkel,
Paul Grayburn,
Ralph Shohet,
期刊:
Circulation: Journal of the American Heart Association
(OVID Available online 2003)
卷期:
Volume 108,
issue 8
页码: 1022-1026
ISSN:0009-7322
年代: 2003
出版商: OVID
关键词: echocardiography;gene therapy;ultrasonics;contrast media
数据来源: OVID
摘要:
Background—Noninvasive, tissue-specific delivery of therapeutic agents would be a valuable clinical tool. We have previously shown that ultrasound-targeted microbubble destruction can direct expression of an adenoviral reporter to the heart. The present study shows that this method can be applied to selectively deliver plasmid vectors to the heart.Methods and Results—We used albumin and lipid microbubbles containing plasmids with a luciferase transgene to target the heart in rats. After 4 days, organs were harvested and analyzed for reporter gene expression. In a second set of experiments, the hearts of rats treated with plasmids were harvested at various time points during a 4-week period. Both luciferase activity and mRNA concentrations were measured. Luciferase transfection with plasmids showed highly specific gene expression in the heart, with hardly any activity in control organs. Time course evaluation showed high transgene expression in the first 4 days, with a rapid decline thereafter. Repeated treatment produced a second peak of transgene expression with similar decay.Conclusions—Ultrasound-mediated destruction of microbubbles directs plasmid transgene expression to the heart with much greater specificity than viral vectors and can be regulated by repeated treatments. This noninvasive technique is a promising method for cardiac gene therapy.
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