Bajgelman Marcio C, Strauss Bryan E
Viral Vector Group, Laboratory of Genetics and Molecular Cardiology/LIM 13, Heart Institute (InCor), University of Sao Paulo School of Medicine, Brazil.
Virology. 2008 Feb 5;371(1):8-13. doi: 10.1016/j.virol.2007.11.015.
Here we introduce a new adenoviral vector where transgene expression is driven by p53. We first developed a synthetic promoter, referred to as PGTxbeta, containing a p53-responsive element, a minimal promoter and the first intron of the rabbit beta-globin gene. Initial assays using plasmid-based vectors indicated that expression was tightly controlled by p53 and was 5-fold stronger than the constitutive CMV immediate early promoter/enhancer. The adenoviral vector, AdPG, was also shown to offer p53-responsive expression in prostate carcinoma cells LNCaP (wt p53), DU-145 (temperature sensitive mutant of p53) and PC3 (p53-null, but engineered to express temperature-sensitive p53 mutants). AdPG served as a sensor of p53 activity in LNCaP cells treated with chemotherapeutic agents. Since p53 can be induced by radiotherapy and chemotherapy, this new vector could be further developed for use in combination with conventional therapies to bring about cooperation between the genetic and pharmacologic treatment modalities.
在此，我们介绍一种新的腺病毒载体，其中转基因表达由p53驱动。我们首先开发了一种合成启动子，称为PGTxbeta，它包含一个p53反应元件、一个最小启动子和兔β-珠蛋白基因的第一个内含子。使用基于质粒的载体进行的初步试验表明，表达受p53严格控制，且比组成型巨细胞病毒立即早期启动子/增强子强5倍。腺病毒载体AdPG在前列腺癌细胞LNCaP（野生型p53）、DU-145（p53温度敏感突变体）和PC3（p53缺失，但经工程改造表达温度敏感p53突变体）中也显示出p53反应性表达。AdPG用作经化疗药物处理的LNCaP细胞中p53活性的传感器。由于p53可由放疗和化疗诱导，这种新载体可进一步开发，与传统疗法联合使用，以实现基因治疗和药物治疗方式之间的协同作用。
