Spatial and temporal control of gene therapy using ionizing radiation

Dennis E. Hallahan, Helena J. Mauceri, Lisa P. Seung, Edward J. Dunphy, Jeffrey D. Wayne, Nader N. Hanna, Alicia Toledano, Samuel Hellman, Donald W. Kufe, Ralph R. Weichselbaum

Research output: Contribution to journalArticle

297 Scopus citations

Abstract

Activation of transcription of the Egr-1 gene by X-rays is regulated by the promoter region of this gene. We linked the radiation-inducible promoter region of the Egr-1 gene to the gene encoding the radiosensitizing and tumoricidal cytokine, tumour necrosis factor-a (TNF-a) and used a replication-deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in nude mice. Combined treatment with AdS.Egr- TNF and 5, 000 cGy (rad) resulted in increased intratumoral TNF-a production and increased tumour control compared with treatment with Ad5.Egr-TNF alone or with radiation alone. The increase in tumour control was achieved without an increase in normal tissue damage when compared to tissue injury from radiation alone. Control of gene transcription by iodizing radiation in vivo represents a novel method of spatial and temporal regulation of gene-based medical treatments.

Original languageEnglish (US)
Pages (from-to)786-791
Number of pages6
JournalNature Medicine
Volume1
Issue number8
DOIs
StatePublished - Aug 1995

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hallahan, D. E., Mauceri, H. J., Seung, L. P., Dunphy, E. J., Wayne, J. D., Hanna, N. N., Toledano, A., Hellman, S., Kufe, D. W., & Weichselbaum, R. R. (1995). Spatial and temporal control of gene therapy using ionizing radiation. Nature Medicine, 1(8), 786-791. https://doi.org/10.1038/nm0895-786