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

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 inte...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1996-03, Vol.56 (5), p.1050-1055
Main Authors: NISHI, T, YOSHIZATO, K, USHIO, Y, YAMASHIRO, S, TAKESHIMA, H, SATO, K, HAMADA, K, KITAMURA, I, YOSHIMURA, T, SAYA, H, KURATSU, J.-I
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biotechnology
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Carotid Artery, Internal - pathology
Electroporation
Escherichia coli - genetics
Fundamental and applied biological sciences. Psychology
Gene therapy
Gene Transfer Techniques
Genetic Therapy - methods
Glioma - genetics
Glioma - pathology
Glioma - therapy
Health. Pharmaceutical industry
Industrial applications and implications. Economical aspects
Lac Operon - genetics
Neoplasm Transplantation
Plasmids - genetics
Plasmids - therapeutic use
Rats
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Summary: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 cell 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 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.
ISSN:0008-5472
1538-7445