1. ¹Cardiovascular Research Unit, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK
2. ²Bracco Research SA, Geneva, Switzerland

Correspondence: Dr CMH Newman, Room OU106, O Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. E-mail: c.newman@sheffield.ac.uk

Received 28 September 2006; Revised 8 January 2007; Accepted 9 January 2007.

Abstract

Ultrasound exposure (USE) in the presence of microbubbles (MCB) (e.g. contrast agents used to enhance ultrasound imaging) increases plasmid transfection efficiency in vitro by several orders of magnitude. Formation of short-lived pores in the plasma membrane ('sonoporation'), up to 100 nm in effective diameter lasting a few seconds, is implicated as the dominant mechanism, associated with acoustic cavitation. Ultrasound enhanced gene transfer (UEGT) has also been successfully achieved in vivo, with reports of spatially restricted and therapeutically relevant levels of transgene expression. Loading MCB with nucleic acids and/or disease-targeting ligands may further improve the efficiency and specificity of UEGT such that clinical testing becomes a realistic prospect.