Gene Transfection By Microbubble-mediated Ultrasound Cavitation

Gene therapy has many irreplaceable advantages and application prospects.Meanwhile, gene therapy is facing many problems and challenges. As macromolecules,genes are difficult to be delivered into the cell, which is the most crucial step for genetherapy. Among various approaches to achieve gene delivery, best transfectionefficiency comes from viral vectors. But because of high risks, gene therapy byviral vector has to be limited in clinical treatment. Other approaches currentlyavailable cannot meet the requirement of safety and efficiency simultaneouslyeither.Thus, a lot of work has been put into discovering safer and more efficient ways ofgene transfection. With the development of ultrasound (US) technology and ultrasoundcontrast agents (UCA) technology in recent years, the method of combining US withUCA to transfect cells has been paid great attention. In practice, different output of USleads to different transfection efficiency. Thus, people normally conduct numerousexperiments by different US settings, to seek the optimal conditions for sonoporation.However， this optimization process highly depends on particular experimentalconditions, and the process is slow.The purpose of this work is to improve the optimization process, and byaccumulating data of each experiment to further optimize the sonoporation technologyof US combined with UCA. The core improvement is to measure the actual ultrasonicparameters of the cell vicinity, which should be more direct and effective index forsonoporation.Results from this study show that microbubbles or UCA can enhancesonoporation, and the transfection efficiency is closely correlated with thepeak-negative acoustic pressures in the ultrasound field. And our resultsindicate that the approach proposed in this study can efficiently optimizeultrasonic parameters for effective sonoporation.