title: Spatial and acoustic pressure dependence of microbubble-mediated gene delivery targeted using focused ultrasound.
abstract: BACKGROUND
  Ultrasound/microbubble-mediated gene delivery has the potential to be targeted to tissue deep in the body by directing the ultrasound beam following vector administration. Application of this technology would be minimally invasive and benefit from the widespread clinical experience of using ultrasound and microbubble contrast agents. In this study we evaluate the targeting ability and spatial distribution of gene delivery using focused ultrasound.
  
  
  METHODS
  Using a custom-built exposure tank, Chinese hamster ovary cells in the presence of SonoVue microbubbles and plasmid encoding beta-galactosidase were exposed to ultrasound in the focal plane of a 1 MHz transducer. Gene delivery and cell viability were subsequently assessed. Characterisation of the acoustic field and high-resolution spatial analysis of transfection were used to examine the relationship between gene delivery efficiency and acoustic pressure.
  
  
  RESULTS
  In contrast to that seen in the homogeneous field close to the transducer face, gene delivery in the focal plane was concentrated on the ultrasound beam axis. Above a minimum peak-to-peak value of 0.1 MPa, transfection efficiency increased as acoustic pressure increased towards the focus, reaching a maximum above 1 MPa. Delivery was microbubble-dependent and cell viability was maintained.
  
  
  CONCLUSIONS
  Gene delivery can be targeted using focused ultrasound and microbubbles. Since delivery is dependent on acoustic pressure, the degree of targeting can be determined by appropriate transducer design to modify the ultrasound field. In contrast to other physical gene delivery approaches, the non-invasive targeting ability of ultrasound makes this technology an attractive option for clinical gene therapy.
authors.affiliation: The Institute of Cancer Research, Gene Therapy Group, Department of Cell and Molecular Biology, 237 Fulham Road, Chelsea, London SW3 6JB, UK. ahad.rahim@icr.ac.uk
authors.forename: Ahad A
authors.initials: AA
authors.lastname: Rahim
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Taylor
authors.forename: Nigel L
authors.initials: NL
authors.lastname: Bush
authors.forename: Gail R
authors.initials: GR
authors.lastname: ter Haar
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Bamber
authors.forename: Colin D
authors.initials: CD
authors.lastname: Porter
mesh_terms: D000162:Acoustics; D000818:Animals; D016466:CHO Cells; D002470:Cell Survival; D006224:Cricetinae; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D045423:Microbubbles; D010957:Plasmids / Q000235:genetics; D011312:Pressure; D014465:Ultrasonics; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D001616:beta-Galactosidase