Abstract—

Uterine leiomyoma (UL) is the most common benign tumor in women of reproductive age. Gene therapy using suicidal genes appears to be a promising approach for UL treatment. One of key factors for success of gene therapy is the right choice of genetic construct carrier. A promising group of non-viral carriers for cell delivery of expression vectors is cationic Cys-flanked peptides which form tight complexes with DNA due to electrostatic interactions and the presence of interpeptide disulfide bonds. The paper reports a comparative study of the physico-chemical, toxic, and transfectional properties of the DNA-peptide complexes obtained by matrix polymerization or oxidative polycondensation of Cys-flanked peptides using the chain growth terminator 2-amino ethanethiol. We have demonstrated the therapeutic effect of the delivery of the pPTK-1 plasmid carrying the herpes simplex virus type 1 (HSV-1) thymidine kinase gene into PANC-1, and HEK-293T cell culture as well as into primary UL cells. It has been shown that the carriers obtained by oxidative polycondensation transform primary UL cells more efficiently than those produced by matrix polymerization. Treatment with ganciclovir resulted in the death of up to 40% of UL cells transfected with the pPTK-1 plasmid. The perspectives of use of the polyR6 carrier produced by oxidative polycondensation as a tool for the development of modular peptide carriers for the purposes of UL gene therapy were discussed.

中文翻译：

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半胱氨酸侧翼阳离子肽用于单纯疱疹病毒胸苷激酶基因的细胞传递，用于子宫平滑肌瘤的自杀基因治疗。

摘要-

子宫平滑肌瘤（UL）是育龄妇女中最常见的良性肿瘤。使用自杀基因的基因治疗似乎是UL治疗的一种有前途的方法。基因治疗成功的关键因素之一是正确选择基因构建载体。可以用于表达载体细胞递送的一组有希望的非病毒载体是阳离子半胱氨酸侧翼肽，其由于静电相互作用和存在肽间二硫键而与DNA形成紧密的复合物。该论文报道了通过使用链增长终止剂2-氨基乙硫醇进行Cys侧翼肽的基质聚合或氧化缩聚获得的DNA肽复合物的理化，毒性和转染特性的比较研究。我们已经证明了携带携带1型单纯疱疹病毒（HSV-1）胸苷激酶基因的pPTK-1质粒进入PANC-1和HEK-293T细胞培养以及原代UL细胞的治疗效果。已经显示，通过氧化缩聚获得的载体比通过基质聚合​​产生的载体更有效地转化初级UL电池。用更昔洛韦治疗导致被pPTK-1质粒转染的UL细胞死亡高达40％。讨论了使用氧化缩聚法生产的polyR6载体作为开发用于UL基因治疗目的的模块化肽载体的工具的观点。已经显示，通过氧化缩聚获得的载体比通过基质聚合​​产生的载体更有效地转化初级UL电池。用更昔洛韦治疗导致被pPTK-1质粒转染的UL细胞死亡高达40％。讨论了使用氧化缩聚法生产的polyR6载体作为开发用于UL基因治疗目的的模块化肽载体的工具的观点。已经显示，通过氧化缩聚获得的载体比通过基质聚合​​产生的载体更有效地转化初级UL电池。用更昔洛韦治疗导致被pPTK-1质粒转染的UL细胞死亡高达40％。讨论了使用氧化缩聚法生产的polyR6载体作为开发用于UL基因治疗目的的模块化肽载体的工具的观点。