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USE OF RAD51 INHIBITORS FOR P53 GENE THERAPY

机译:RAD51抑制剂在P53基因治疗中的应用

摘要

The present invention is directed to methods and compositions for inhibiting or reducing tumor cell proliferation in an individual in vivo. More specifically, a tumor cell is contacted, in vivo, with a Rad51 inhibitor, and a polynucleotide capable of expressing functional p53 protein. In a further embodiment of the present invention the tumor cell is exposed in vivo to radiation or chemotherapeutic agents (e.g., BCNU CCNU, and DMZ, GB, cisplatin and the like). The Rad51 inhibitor may be selected from the group consisting of peptides, small molecules and Rad51 antisense molecules. The Rad51 antisense molecule and the p53 polynucleotide may be encoded on an expression vector under the control of one or more promoters, and the expression vector may then be incorporated into a viral genome, preferably an andeno or retro virus, which is then used to introduce the expression vector into the tumor cell.
机译:本发明涉及在体内抑制或减少肿瘤细胞增殖的方法和组合物。更具体地,使肿瘤细胞在体内与Rad51抑制剂和能够表达功能性p53蛋白的多核苷酸接触。在本发明的另一个实施方案中,将肿瘤细胞体内暴露于放射或化学治疗剂(例如,BCNU CCNU和DMZ,GB,顺铂等)。 Rad51抑制剂可以选自肽,小分子和Rad51反义分子。 Rad51反义分子和p53多核苷酸可在一个或多个启动子的控制下编码在表达载体上,然后可将表达载体掺入病毒基因组中,优选为雄性或逆转录病毒,然后将其用于引入表达载体进入肿瘤细胞。

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