In vivo silencing of a molecular target by short interfering RNA electroporation: Tumor vascularization correlates to delivery efficiency

Yoshifumi Takei, Toshio Nemoto, Ping Mu, Tatsuya Fujishima, Takuji Ishimoto, Yasuhiko Hayakawa, Yukio Yuzawa, Seiichi Matsuo, Takashi Muramatsu, Kenji Kadomatsu

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Screening for a molecular target for cancer therapy requires multiple steps, of which an important one is evaluation of the knockdown effect of the target molecule on pregrown xenograft tumors. However, methods currently used for local administration of knockdown reagents, such as short interfering RNA (siRNA), are not satisfactory as to simplicity and efficiency. We established an electroporation method involving a constant voltage and "plate and fork" type electrodes and used it for in vivo delivery of siRNA. The delivery efficiency correlated to the electric current. The electric current correlated to the microvascular density and vascular endothelial growth factor (VEGF) expression and exhibited a threshold that guaranteed efficient delivery. Consequently, we showed that the vascularization and VEGF expression in tumors determined the efficiency of delivery of siRNA by electroporation. VEGF was chosen as a model target. VEGF siRNA electroporation suppressed the growth of tumors exhibiting high VEGF expression to less than 10% of the control level, but it had no effect on low VEGF-expressing tumors. Notably, a long interval (20 days) of electroporation was enough to obtain a satisfactory effect. Systemically injected siRNA could also be delivered into tumors by this method. Our data will provide the technical basis for in vivo electroporation, and this simple and efficient siRNA delivery method is applicable to in vivo comprehensive screening for a molecular target.

Original languageEnglish
Pages (from-to)211-221
Number of pages11
JournalMolecular Cancer Therapeutics
Volume7
Issue number1
DOIs
Publication statusPublished - 01-01-2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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