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

296 Citations (Scopus)

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

Fingerprint

Gene therapy
Ionizing radiation
Ionizing Radiation
Genetic Therapy
Genes
Radiation
Tumors
Transcription
Genetic Promoter Regions
Tumor Necrosis Factor-alpha
Tissue
Gene encoding
Neoplasms
Radiation Injuries
Adenoviridae
Nude Mice
Transcriptional Activation
Chemical activation
Cytokines
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hallahan, D. E., Mauceri, H. J., Seung, L. P., Dunphy, E. J., Wayne, J. D., Hanna, N. N., ... 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
Hallahan, Dennis E. ; Mauceri, Helena J. ; Seung, Lisa P. ; Dunphy, Edward J. ; Wayne, Jeffrey D. ; Hanna, Nader N. ; Toledano, Alicia ; Hellman, Samuel ; Kufe, Donald W. ; Weichselbaum, Ralph R. / Spatial and temporal control of gene therapy using ionizing radiation. In: Nature Medicine. 1995 ; Vol. 1, No. 8. pp. 786-791.
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Hallahan, DE, Mauceri, HJ, Seung, LP, Dunphy, EJ, Wayne, JD, Hanna, NN, Toledano, A, Hellman, S, Kufe, DW & Weichselbaum, RR 1995, 'Spatial and temporal control of gene therapy using ionizing radiation', Nature Medicine, vol. 1, no. 8, pp. 786-791. https://doi.org/10.1038/nm0895-786

Spatial and temporal control of gene therapy using ionizing radiation. / Hallahan, Dennis E.; Mauceri, Helena J.; Seung, Lisa P.; Dunphy, Edward J.; Wayne, Jeffrey D.; Hanna, Nader N.; Toledano, Alicia; Hellman, Samuel; Kufe, Donald W.; Weichselbaum, Ralph R.

In: Nature Medicine, Vol. 1, No. 8, 08.1995, p. 786-791.

Research output: Contribution to journalArticle

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AU - Hanna, Nader N.

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AU - Hellman, Samuel

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AU - Weichselbaum, Ralph R.

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Hallahan DE, Mauceri HJ, Seung LP, Dunphy EJ, Wayne JD, Hanna NN et al. Spatial and temporal control of gene therapy using ionizing radiation. Nature Medicine. 1995 Aug;1(8):786-791. https://doi.org/10.1038/nm0895-786