Abstract
Gene therapy has continuously evolved throughout the years since its first proposal to develop more specific and effective transfection, capable of treating a myriad of health conditions. Viral vectors are some of the most common and most efficient vehicles for gene transfer. However, the safe and effective delivery of gene therapy remains a major obstacle. Ultrasound contrast agents in the form of microbubbles have provided a unique solution to fulfill the need to shield the vectors from the host immune system and the need for site specific targeted therapy. Since the discovery of the biophysical and biological effects of microbubble sonification, multiple developments have been made to enhance its applicability in targeted drug delivery. The concurrent development of viral vectors and recent research on dual vector strategies have shown promising results. This review will explore the mechanisms and recent advancements in the knowledge of ultrasound-mediated microbubbles in targeting gene and drug therapy.
Highlights
Cancer is currently the second major cause of death in the United States (USA).Despite increasing research investment and new therapeutic developments, overall cancer death rates have improved only modestly in the past 20 years in the US, from 200.7 per100,000 people in 1999 to 149.2 per 100,000 people in 2018 [1]
The bulk stream is important in gene therapy applications, since distance between MBs and the target cell membrane has been observed to influence the degree of pore formation in previous studies [23,24]
The authors demonstrated that when the region of interest is sonificated, ultrasound radiation forces lead to unfolding of the polyethylene glycol (PEG) chain and exposure of the ligand to the specific target
Summary
Cancer is currently the second major cause of death in the United States (USA). Despite increasing research investment and new therapeutic developments, overall cancer death rates have improved only modestly in the past 20 years in the US, from 200.7 per. Viral-based transduction is classified as stable or transient transfection In the former, upon entering the host cell, the viral genetic material is integrated into the host cell genome, and the new addition is continuously expressed through the subsequent cell progeny. Retroviruses typically exhibit lower rates of host inflammation than adenovirus and herpes virus; stable transfection is associated with a high risk of insertional mutagenesis and gene disruption, and retroviruses are limited by the ability to only infect dividing cells [5]. Given the advantages and disadvantages of non-viral and viral-based vectors, one of the main challenges in gene delivery has been the development of a delivery system that is consistently safe and efficacious for clinical application. A recently developed approach to overcome these obstacles and generate targeted and safe transfection with reduced risk of host immunogenicity is the use of an ultrasound-guided microbubbles (MBs) delivery system. This article explores the current developments and prospective research in targeted delivery of gene therapy using MBs ultrasound contrast agents
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