Herpes Simplex Virus Thymidine Kinase-Mediated Suicide Gene Therapy Using Nano/Microbubbles and Ultrasound

Atsuko Aoi, Yukiko Watanabe, Shiro Mori, Masahiko Takahashi, Georges Vassaux, Tetsuya Kodama

研究成果: Article査読

69 被引用数 (Scopus)

抄録

A physical method using ultrasound (US) and nano/microbubbles (NBs) can deliver exogenous molecules noninvasively into a specific target site. In this study, we evaluated the application of this technology to cancer gene therapy using prodrug activation therapy. Low-intensity pulsed ultrasound (1 MHz; 1.3 W/cm2) and NBs were used to transduce the herpes simplex thymidine kinase (HSVtk) gene in vitro, leading to gene transfer. The addition of ganciclovir (GCV) to the transduced cells led to HSVtk/GCV-dependent cell death mediated by apoptosis. This technology was then assessed in vivo, using mice bearing subcutaneous tumors (1 MHz; 3.0 W/cm2). Gene transfer to the tumor, measured by luciferase activity, was transient, with a peak of expression 24 h after transduction, and decreased at 48 h, demonstrating the transient nature of US/NB-mediated gene transfer. The therapeutic potential of this approach was evaluated through repeated intratumoral gene delivery using US/NB-mediated transfer of the HSVtk gene, followed by recurrent administration of GCV, using two different experimental treatment protocols. In both cases, dramatic reductions of the tumor size by a factor of four were observed. Altogether, these data demonstrate the potential of US/NB as a new physical gene delivery method for cancer gene therapy. (E-mail: kodama@tubero.tohoku.ac.jp).

本文言語English
ページ(範囲)425-434
ページ数10
ジャーナルUltrasound in Medicine and Biology
34
3
DOI
出版ステータスPublished - 2008 3

ASJC Scopus subject areas

  • Biophysics
  • Radiological and Ultrasound Technology
  • Acoustics and Ultrasonics

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