梭状芽孢杆菌
生物
基因
遗传增强
基因表达
癌症研究
肿瘤坏死因子α
电离辐射
分子生物学
重组DNA
免疫学
辐照
细菌
遗传学
物理
核物理学
作者
Sandra Nuyts,Lieve Van Mellaert,Jan Theys,Willy Landuyt,Eugène Bosmans,Jozef Anné,Philippe Lambin
出处
期刊:Gene Therapy
[Springer Nature]
日期:2001-08-01
卷期号:8 (15): 1197-1201
被引量:92
标识
DOI:10.1038/sj.gt.3301499
摘要
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 TNFalpha 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 TNFalpha 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 TNFalpha 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.
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