Novel gene switches for targeted and timed expression of proteins of interest
Novel gene switches for targeted and timed expression of proteins of interest
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DOI：
10.1016/j.ymthe.2005.03.029
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发表时间：
2005-08-01
影响因子：
12.4
通讯作者：
Voellmy, R
中科院分区：
文献类型：
--
作者：
Vilaboa, N;Fenna, M;Voellmy, R
本文报道了新型基因开关的体外和体内构建和分析，该开关可用于实现对感兴趣的转基因表达的空间和时间控制。这些开关预计可在几乎任何组织和细胞类型中发挥作用。它们由(a)在响应热和反式激活子的启动子或启动子盒的双重控制下表达的外源或修饰的反式激活子和(b)响应反式激活子以控制目的转基因的启动子组成。这种类型的优选基因开关掺入了米非司酮依赖性反式激活因子。在米非司酮存在的情况下，这种基因开关可以通过瞬时热处理来激活。活性随着活化热处理的强度而增加，并且被发现可以持续超过 6 天。在米非司酮存在或不存在的情况下，在激活热处理之前，基因开关基本上处于失活状态。激活的基因开关可以通过去除/撤回米非司酮来沉默。
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.