肿瘤自杀基因靶向治疗

摘要

Suicide gene therapy is an important method of gene therapy for cancer.It has been successfully used in a large number of in vitro and in vivo studies.The two major suicide gene therapeutic strategies currently pursued are:herpes simplex virus thymidine kinase/ganciclovir(HSV-tk/GCV)and cytosine deaminase/5 -fluorocytosine(CD/5-FC).In this review,we summarize the different suicide gene systems and gene delivery vectors addressed to canc-er,and the different strategies that have been used with suicide gene therapy and provide some insights into the future directions of this approach,particularly towards nanoparticle carrier and cancer stem cells.%自杀基因靶向疗法在恶性肿瘤的治疗方法中占有重要的位置。众多体内体外试验已经证明了自杀基因的肿瘤杀伤效应。目前，相关的临床试验也证实HSV-tk/GCV，CD/5-FC等自杀基因系统具有良好的抗肿瘤效应。然而在临床推广应用上还有很多问题需要解决，如基因靶向转移困难、基因转染效率较低、基因转移后的表达缺乏有效的调控手段和基因杀伤效应较低且难以控制等，这些问题均有待于我们在今后的研究中进一步解决。本文将从自杀基因的种类、载体、作用机制、旁观者效应和临床发展前景，尤其是纳米粒载体和肿瘤干细胞理论的应用等方面进行综述。