Amplification of transgene expression in vitro and in vivo using a novel inhibitor of histone deacetylase.
Amplification of transgene expression in vitro and in vivo using a novel inhibitor of histone deacetylase.
复制标题
使用新型组蛋白脱乙酰酶抑制剂在体外和体内扩增转基因表达。
作者：
T. Yamano;K. Ura;R. Morishita;H. Nakajima;M. Monden;Y. Kaneda
增强转基因表达是人类基因治疗中的一个重要问题。在这里，我们描述了一种新的系统，用于增强转基因表达的质粒DNA与FR 901228，一种水溶性组蛋白去乙酰化酶抑制剂共引入。当将荧光素酶表达载体与FR 901228共同引入细胞中时，与没有药物的细胞相比，荧光素酶基因表达在小鼠黑素瘤细胞系B16-F1中增强50倍，在NIH 3 T3细胞中增强5200倍。荧光素酶基因表达增强依赖于药物剂量和治疗时间。乙酰化组蛋白的增加与药物剂量一致，基因表达的激活发生在转录水平。在稳定表达荧光素酶的B16-F1克隆中也观察到FR 901228对荧光素酶基因表达的刺激。将荧光素酶质粒与FR 901228共导入B16-F1肿瘤块中激活荧光素酶基因表达3- 4倍。因此，FR 901228激活转基因表达可能成为基因治疗的新工具。
Enhancement of transgene expression is an important issue in human gene therapy. Here we describe a novel system for enhancing transgene expression by cointroduction of plasmid DNA with FR901228, a water-soluble histone deacetylase inhibitor. When a luciferase expression vector was cointroduced into cells with FR901228, luciferase gene expression was enhanced 50-fold in the mouse melanoma cell line B16-F1 and 5200-fold in NIH3T3 cells in comparison to cells without the drug. Luciferase gene expression enhancement was dependent on both drug dose and treatment time. Acetylated histones increased in accordance with drug dose, and the activation of gene expression occurred at the transcriptional level. The stimulation of luciferase gene expression by FR901228 was also observed in a B16-F1 clone stably expressing luciferase. Cointroduction of the luciferase plasmid with FR901228 into a B16-F1 tumor mass activated luciferase gene expression 3- to 4-fold. Thus, activation of transgene expression by FR901228 may serve as a new tool for gene therapy.
DOI：
10.1073/pnas.88.4.1330
发表时间：
1991-02-01
影响因子：
11.1
作者：
PALMER, TD;ROSMAN, GJ;MILLER, AD
通讯作者：
MILLER, AD
DOI：
10.1073/pnas.94.11.5798
发表时间：
1997-05-27
影响因子：
11.1
作者：
Chen, WY;Bailey, EC;Townes, TM
通讯作者：
Townes, TM