Ultrasound-enhanced gene transfection: vectors, methods, and biomedical applications

Gene therapy relying on the efficiency of gene delivery or transfection has become a widely applied approach in numerous biomedical fields. Ultrasound, featuring non-invasive and deep tissue penetration nature, offers effective enhancement treatment with precise targeting and minimal side effects. Here, we critically analyze the vectors, methods, and biomedical applications of ultrasound-enhanced gene transfection. Firstly, the therapeutic potential of ultrasound lies in its synergistic thermal, cavitation, and mechanical effects. Secondly, various vectors, both viral and non-viral, are available for delivering therapeutic genes. Additionally, techniques like sonoporation, sonodynamic effect, and ultrasound-targeted microbubble destruction enable the precise delivery of bioactive genes to targeted tissues. We particularly highlight the diverse biomedical applications of ultrasound-enhanced gene transfection across different disease areas, including cancer, cardiac insufficiency, stroke, neurodegenerative disease, and musculoskeletal disorders, demonstrating promising prospects for clinical application. Finally, we systematically address the current challenges and perspectives to inform the design of ultrasound-enhanced gene transfection compared to conventional gene therapies. This review aims to guide new developments in ultrasound-enhanced gene transfection and contribute to its widespread utilization in biomedical applications.