Published online before print August 11, 2003, doi: 10.1161/01.CIR.0000084535.35435.AE
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(Circulation. 2003;108:1022.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Ultrasound-Targeted Microbubble Destruction Can Repeatedly Direct Highly Specific Plasmid Expression to the Heart
From the Department of Internal Medicine (R.B., R.V.S.), University of Texas Southwestern Medical Center, VA Medical Center (P.A.F.), and Baylor Heart and Vascular Institute (S.C., P.A.G.), Dallas, Tex.
Correspondence to Ralph V. Shohet, MD, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, NB 11.200, Dallas, TX 75390-8573. E-mail ralph.shohet{at}utsouthwestern.edu
Received January 3, 2003; de novo received March 11, 2003; revision received April 16, 2003; accepted April 25, 2003.
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.
Key Words: echocardiography • gene therapy • ultrasonics • contrast media
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