Novel gene switches for targeted and timed expression of proteins of interest

被引：38
作者：
Vilaboa, N
Fenna, M
Munson, J
Roberts, SM
Voellmy, R [1 ]
机构：
[1] Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA
[2] Univ Florida, J Hillis Miller Hlth Sci Ctr, Ctr Environm & Human Toxicol, Gainesville, FL 32611 USA
[3] HSF Pharmaceut SA, CH-1009 Pully, Switzerland
[4] Hosp Univ La Paz, Lab Metab Oseo, Madrid 28046, Spain
来源：
MOLECULAR THERAPY | 2005年 / 12卷 / 02期
基金：
美国国家卫生研究院;
关键词：
gene switches; gene therapy; transcriptional targeting; heat shock protein;
D O I：
10.1016/j.ymthe.2005.03.029
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
This article reports on the construction and analysis in vitro and in vivo of novel gene switches that can be used to achieve spatial as well as temporal control over the expression of a transgene of interest. The switches are expected to be functional in virtually any tissue and cell type. They consist of (a) a foreign or modified transactivator expressed under the dual control of a promoter or promoter cassette that is responsive to heat and the transactivator and (b) a promoter responsive to the transactivator for controlling the transgene of interest. A preferred gene switch of this type incorporated a mifepristone-dependent transactivator. This gene switch could be activated by a transient heat treatment in the presence of mifepristone. Activity increased with the intensity of the activating heat treatment and was found to persist for more than 6 days. The gene switch was essentially inactive prior to an activating heat treatment, in the absence or presence of mifepristone. Activated gene switch could be silenced by removal/withdrawal of mifepristone.
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收藏
页码：290 / 298
页数：9
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