Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences
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DOI:
10.1038/6981
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发表时间:
1999-03-01
影响因子:
46.9
通讯作者:
Draghia-Akli, R
Draghia-Akli, R
中科院分区:
工程技术1区
文献类型:
--
作者:
Li, XY;Eastman, EM;Draghia-Akli, R

文献摘要

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天然存在的启动子表达水平相对较低,限制了肌肉作为基因治疗靶点的应用。生肌限制性基因启动子显示复杂的组织,通常涉及几个生肌调控元件的组合。通过将E-box、MEF-2、TEF-1和SRE位点随机组装到合成启动子重组文库中,并筛选数百个单独克隆的体外和体内转录活性,分离出几种人工启动子,其转录效力大大超过天然肌源性和病毒基因启动子。
Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity in vitro and in vivo, several artificial promoters were isolated whose transcriptional potencies greatly exceed those of natural myogenic and viral gene promoters.