Ultrasound-targeted microbubble destruction in gene therapy: A new tool to cure human diseases

Abstract

Human gene therapy has made significant advances in less than two decades. Within this short period of time, gene therapy has proceeded from the conceptual stage to technology development and laboratory research, and finally to clinical trials for the treatment of a variety of deadly diseases. Cardiovascular disease, cancer, and stroke are leading causes of death worldwide. Despite advances in medical, interventional, radiation and surgical treatments, the mortality rate remains high, and the need for novel therapies is great. Gene therapy provides an efficient approach to disease treatment. Notable advances in gene therapy have been made for genetic disorders, including severe combined immune deficiency, chronic granulomatus disorder, hemophilia and blindness, as well as for acquired diseases, including cancer and neurodegenerative and cardiovascular diseases. However, lack of an efficient delivery system to target cells as well as the difficulty of sustained expression of transgenes has hindered advancements in gene therapy. Ultrasound targeted microbubble destruction (UTMD) is a promising approach for target-specific gene delivery, and it has been successfully investigated for the treatment of many diseases in the past decade. In this paper, we review UTMD-mediated gene delivery for the treatment of cardiovascular diseases, cancer and stroke.

Ultrasound‑targeted microbubble destruction‑mediated miR‑767 inhibition suppresses tumor progression of non‑small cell lung cancer

“…Additionally, gene transfer by UTMD can avoid degradation by lytic enzymes (15). The application of UTMD has been highlighted in cancer treatment, which greatly contributes to targeted cancer therapy (16).…”

Microbubbles and Nanobubbles with Ultrasound for Systemic Gene Delivery

“…Ultrasound exposure is known to increase cell membrane permeability and facilitate the delivery of drugs or genes into cells [ 18 , 19 ]. A combination of ultrasound exposure and microbubbles further increases cell membrane permeability even when using weak intensity ultrasound, leading to enhanced drug and gene uptake [ 12 , 13 , 14 , 15 , 16 , 17 ]. Stable oscillations of microbubbles are caused by exposure to low acoustic pressure, a process termed stable cavitation.…”

“…In recent years, nanoscale contrast agents have been developed. Furthermore, micro- or nanobubbles have previously been investigated as site-specific drug or gene delivery tools [ 12 , 13 , 14 , 15 , 16 , 17 ]. To exploit the combination of ultrasound and bubbles both for diagnosis and therapeutics as a theranostic system, various types of bubbles valuable for systemic administration have been well documented in recent years.…”

Ultrasound-Targeted Microbubble Destruction Enhances the Inhibitive Efficacy of miR-21 Silencing in HeLa Cells

“…The technology mainly uses microbubbles to localize a “blast” using ultrasound irradiation to release the genes it carries [ 7 , 8 ]. At the same time, the shock caused by ultrasonic and microbubble rupture increases local cell permeability, generates reversible acoustic pores, and promotes the entry of genes into the nucleus, which can improve the transfection and expression efficiency of genes [ 9 ]. Secondly, the protection of microbubbles can prevent the carried genes or drugs from being degraded by the endonucleases in the plasma, so that they can stably reach the target organ or tissue through blood circulation [ 10 ].…”