Abstract
Ultrasound-targeted microbubble destruction (UTMD) is a non-invasive technique for gene delivery, utilizing high power ultrasound and nucleic acid-bearing microbubbles. UTMD has been used in a variety of in vivo applications, including cardiac and skeletal muscle, kidney, liver, cerebral and even lung, and have been studied using many gene vectors, including plasmid, viral and small interfering RNA. The focus of gene therapy has now shifted towards small non-coding RNAs, including microRNAs (miRNA). These non-coding RNAs are important transcriptional and post-transcriptional inhibitors of gene expression that regulate the translational output of target messenger RNAs. MicroRNAs have been shown to participate in a multitude of cellular process, and their dysregulation may play an important pathophysiologic role in many different human pathologies. Coupled with their ability to specifically target particular cellular pathways, makes the possibility of exploiting miRNAs to develop therapeutic strategies extremely attractive. This presentation will focus specifically on several miRNAs with UTMD applications in (1) chronic ischemic peripheral arterial disease, (2) ischemia-reperfusion injury, and (3) abdominal aortic aneurysms (AAA). For each application, we will discuss selection of miRNA, aspects of tissue targeting in vivo, enhancement of therapeutic effect and potential for clinical translation.
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