High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation

Toru Nishi, Kimio Yoshizato, Shigeo Yamashiro, Hideo Takeshima, Kyoichi Sato, Kazuya Hamada, Isao Kitamura, Teizo Yoshimura, Hideyuki Saya, Jun Ichi Kuratsu, Yukitaka Ushio

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Abstract

A novel method for high-efficiency and region-controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery of rats whose brain tumors (from prior inoculation) had been electroporated between two electrodes. The lacZ gene was efficiently transferred and expressed in the tumor cells 3 days after plasmid injection. However, neither any gene transfers nor any elevated lacZ activity was detected in tissues outside the electrodes. The plasmid was not transferred without electroporation. Human monocyte chemoattractant protein-1 cDNA was also transferred by this method, and its long-lasting (3 weeks) expression was confirmed by using the Epstein-Barr virus episomal replicon system. The expressed monocyte chemoattractant protein-1 protein was functional, as evident by the presence of a large number of monocytes in the tumor tissue. This method, 'electrogene therapy,' which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy.

Original languageEnglish
Pages (from-to)1050-1055
Number of pages6
JournalCancer Research
Volume56
Issue number5
Publication statusPublished - Mar 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Nishi, T., Yoshizato, K., Yamashiro, S., Takeshima, H., Sato, K., Hamada, K., Kitamura, I., Yoshimura, T., Saya, H., Kuratsu, J. I., & Ushio, Y. (1996). High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation. Cancer Research, 56(5), 1050-1055.