Key result
Ultrasound-targeted microbubble destruction enables organ-specific cardiac transgene expression peaking within the first 4 days.
Why the study?
Noninvasive, tissue-specific delivery of therapeutic agents to the heart is a valuable clinical tool, and methods for selective plasmid vector delivery to the heart need evaluation.
May advance targeted cardiac gene delivery in preclinical models; hypothesis-generating and should not yet change practice.
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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Bekeredjian et al. (2003) studied this question. Ultrasound-targeted microbubble destruction with plasmid vectors vs. Control organs was evaluated on Reporter gene expression (luciferase activity and mRNA concentrations). Ultrasound-targeted microbubble destruction directed highly specific plasmid transgene expression to the rat heart, peaking in the first 4 days and capable of being regulated by repeated treatments.
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