Title: Radio-responsive recA promoter significantly increases TNF alpha production in recombinant clostridia after 2 Gy irradiation
Authors: Nuyts, Sandra ×
Van Mellaert, Lieve
Theys, Jan
Landuyt, W
Bosmans, Eugene
Anné, Jozef
Lambin, Philippe #
Issue Date: Aug-2001
Publisher: Nature publishing group
Series Title: Gene therapy vol:8 issue:15 pages:1197-1201
Abstract: One of the major problems with gene therapy today is the lack of tumour specificity. The use of anaerobic apathogenic clostridia as a gene transfer system can target anoxic areas within the tumour. These bacteria can be genetically modified to express therapeutic proteins such as TNF alpha locally in the tumour. As shown in our results, ionising irradiation can be used in clostridia to activate genes encoding cytotoxic agents under control of a radiation-inducible promoter. A 44% significant increase (P < 0.05) in TNF<alpha> secretion was seen 3.5 h after a single dose of 2 Gy. A second dose of 2 Gy was also capable of repeating gene activation and gave a significant increase of TNF alpha production of 42% (P < 0.05). These results provide evidence that spatial and temporal control of gene expression can be achieved using a radio-inducible promoter. Repetitive gene activation was feasible with a second dose of 2 Gy, indicating that fractionated radiotherapy could lead to repeated gene induction resulting in prolonged and enhanced protein expression. Gene targeting by ionising radiation could thus provide a new means of increasing the therapeutic ratio in cancer treatment.
ISSN: 0969-7128
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Bacteriology (Rega Institute)
Laboratory of Experimental Radiotherapy
× corresponding author
# (joint) last author

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