【作者】 安丽娜；

【导师】 王树人；

【作者基本信息】 四川大学 ， 病理学与病理生理学， 2006， 硕士

【摘要】 近年来，随着肿瘤基因治疗的兴起，自杀基因疗法逐渐成为研究的热点之一，其中胞嘧啶脱氨酶／5—氟胞嘧啶(Cytosine Deaminase／5-Fluorocytosine，CD／5-FC)系统是近年来得到广泛关注的自杀基因系统，并已被证实具有抗肿瘤作用。然而该治疗系统还存在许多亟待解决的问题，如在体内基因转化效率较低、部分肿瘤细胞对5—FC不敏感、缺乏肿瘤特异性载体等。这些困难严重限制了该治疗系统的发展及向临床应用的转化，为解决这一问题我们设计了一个全新的方案：即在本实验室已成功构建的CD／5-FC自杀基因疗法的基础上引入哺乳动物所缺乏的尿嘧啶磷酸核糖转移酶(Uracil Phosphoribosyltransferase，UPRT)基因，以非致病婴儿双歧杆菌作为载体，利用实体瘤内低氧代谢的特点和厌氧菌趋低氧环境的更多还原

【Abstract】 With the advancing of tumor gene therapy, suicide gene therapy has become a highlight in tumor therapy field nowadays. Cytosine Deaminase/5-Fluorocytosine (CD/5-FC) system is one of the most intensely studied gene therapies, and its anti-tumor effect has been experimentally proved . But some disadvantages of this suicide gene system , such as low efficiency of gene transduction, 5-FU resistance in some kind of tumor cells, lack of tumor-targeting gene delivery vectors and so on, are all the important obstacles which greatly restrict its development and clinical application .For tackling these problems , we clone a Uracil Phosphoribosyltransferase (UPRT) gene, which is absent in mammal cells ,into the anaerobicBifidobacterium infantis , combining with the CD/5-FC suicide gene system which has been previously constructed in this Lab, and constructed a novel hypoxia-targeting therapy system with double suicide genes for solid tumor, by using the nonpathogenic anaerobic Bifidobacterium infantis as the vector, which will characteristically colonize in the hypoxic center area of solid tumors. The colonized anaerobic germs can simultaneously express Cytosine Deaminase and Uracil Phosphoribosyltransferase in tumor tissue, which then turn the prodrug 5-FC into the toxic anti-tumor drug. The anti-tumor effects were observed.更多还原