Alekseenko I V, Kuz'min D V, Pleshkan V V, Zinov'eva M V, Sverdlov E D
Bioorg Khim. 2013 Nov-Dec;39(6):745-8. doi: 10.1134/s1068162013060010.
In preparation of the therapeutic genetic constructs aimed to the gene-programmed enzymatic transformation of the non-toxic prodrug into toxin within cancer cells the right choice of regulatory elements (promoters and enhancers) is essential. This is widely accepted that the efficiency of the gene therapy constructions is dependent, in particular, on the strength of promoters driving the expression of the therapeutic genes. In this work we demonstrated, using the melanoma-specific promoters and enhancers of human melanoma inhibitory activity and mouse tyrosinase gene, that for the development of cytotoxic effect the promoter strength is not of primary importance. In the case of HSVtk, coding for the herpes simplex virus thymidine kinase, and FCU1, coding for cytosine deaminase/uracil phosphoribosyltransferase hybrid protein genes, their cytotoxic activity was determined by the quantity of the added prodrug.
在制备旨在将无毒前体药物在癌细胞内进行基因编程酶促转化为毒素的治疗性基因构建体时，正确选择调控元件（启动子和增强子）至关重要。人们普遍认为，基因治疗构建体的效率尤其取决于驱动治疗性基因表达的启动子的强度。在这项工作中，我们使用人类黑色素瘤抑制活性的黑色素瘤特异性启动子和增强子以及小鼠酪氨酸酶基因证明，对于细胞毒性作用的产生，启动子强度并非至关重要。对于编码单纯疱疹病毒胸苷激酶的HSVtk和编码胞嘧啶脱氨酶/尿嘧啶磷酸核糖基转移酶杂合蛋白基因的FCU1，它们的细胞毒性活性由添加的前体药物的量决定。
