Recent advances in gene delivery with ultrasound and microbubbles

Abstract

Recently, microbubbles used in combination with ultrasound has been proposed as an alternative method for in vitro and in vivo gene delivery. Ultrasound (US) and microbubble assisted delivery (USMD) has great clinical potential based on the fact that ultrasound contrast agents (USCAs) are clinically approved for diagnostic applications. The mechanism that supports gene delivery via USMD is thought to be 'sonoporation'. It is hypothesised that the interaction of US and USCA can induce a transient cell membrane permeabilisation leading to enhanced DNA uptake. The exact mechanism(s) of gene uptake remains a subject of academic debate and various hypotheses have been proposed, including acoustic microstreaming or local shear stresses, microjetting and cavitation. This review provides the current understanding of USMD and highlights both the bubble characteristics and ultrasound parameters that support USMD in vitro and in vivo. Both safety and efficacy of gene delivery by sonoporation are discussed. In addition, USMD is compared with electroporation, another widely used physical method for gene delivery.