Extracorporeal shock waves for gene therapy?

Microbubble-enhanced ultrasound for vascular gene delivery

“…30 The involvement of cavitation is further supported by the fact that exposure to lithotripter shock waves, which induce gallstone and kidney stone fragmentation through cavitational mechanisms, is also associated with enhanced transgene expression following naked DNA transfection in vitro. 18,31,32 We and others have previously reported that USE also enhances transgene expression following lipofection in vitro. 15,17,19 USE of porcine VSMC in the presence of Optison had no significant effect upon transgene expression following lipofection using the Promega reagent Tfx-50 according to conditions previously optimised in the absence of microbubbles or ultrasound (Figure 5a), and indeed luciferase activity was lower than that observed with the combination of USE, Optison and naked plasmid DNA (Figures 2 and 4).…”

Emerging Therapeutic Ultrasound

“…The large molecules were found in the surviving cells with a diffuse distribution within the cytoplasm. These observations led to the suggestion that LSW could be used for gene therapy (Delius et al, 1995).…”

“…The observation of permeabilization by Shockwaves led to a suggestion by Delius et al (1995) that extracorporeal Shockwave lithotripsy might be useful for gene therapy. Based on in vitro results at higher frequencies, and even diagnostic ultrasound with contrast agents, many forms of ultrasound appear to be capable of DNA transfer to varying degrees, depending on the cavitation activity obtained.…”

“…As noted above, cancer may be a particularly suitable target for ultrasoundmediated gene therapy. The concept of LSW application for tumor treatment had been explored in the early 1990s, and the possibility of LSW gene therapy was suggested by Delius et al (1995). The efficacy of ultrasound enhanced cancer gene therapy during lithotripsy Shockwave (LSW) treatment was tested with interleukin-12 (IL-12) immunotherapy (Song et al, 2002a).…”

“…In treating cell suspensions, some cells were found to be transiently permeabilized, allowing them to take up large molecules normally excluded by the cell membrane Gambihler et al (1994). This discovery was quickly recognized as a new treatment tool, and lithotripter shock wave (LSW) treatment was proposed as a means of gene therapy (Delius et al, 1995). Although LSWs reliably initiate cavitation activity in vitro and sometimes in vivo, other ultrasound modes can also generate cavitational effects.…”