摘要
基因治疗是指将外源正常基因通过基因转移技术导入靶细胞,纠正或补偿因基因缺陷和异常引起的疾病,以达到治疗目的的一种生物治疗方法。本文从自杀基因、基因沉默、抑癌基因、免疫基因、抑制血管生成基因等几方面综述了近几年肿瘤基因治疗的研究和发展现状。自杀基因治疗系统包括HSV-tk GCV系统、H19 RNA、h TERT等,HSV-tk GCV系统是自杀基因治疗系统研究最多的一种,TK基因是药敏基因,肿瘤细胞转染该基因后,对前体药物丙氧鸟苷(GCV)或无环鸟苷(ACV)变得敏感而能被杀死。RNA干扰是基因沉默治疗的主要方式,通过沉默肿瘤相关基因IDO2、DUSP6、IGF1R、ORAOV1等基因可以明显抑制肿瘤生长。抑癌基因激活或过表达可以抑制肿瘤生长,p53和PTEN是两个最有意义的抑癌基因,重组腺病毒p53和PTEN可以显著抑制肿瘤生长。免疫基因治疗是将细胞因子或共刺激分子基因导入肿瘤细胞或体细胞内,通过激发或调动机体免疫功能来控制或杀伤肿瘤细胞,常用的免疫效应细胞有TIL、CTL、LAK、NK等,可供选择的目的基因有肿瘤坏死因子、白介素、集落刺激因子、干扰素、趋化因子等。抑制血管生成基因可以通过抑制肿瘤新生血管的生成,来阻止肿瘤生长和侵袭,VEGF-Trap、PEDF、ES通过腺病毒导入肿瘤可以显著抑制肿瘤生长。目前肿瘤基因治疗在特异性、安全性和靶向性方面依然存在亟需解决的问题。
Gene therapy is one of biological treatment methods that exogenous normal gene is transferred into target cells by gene transfer technology to correct or compensate for genetic defects or abnormality of diseases in order to achieve the treatment purpose. In this paper,research and development status of tumor gene therapy in recent years were reviewed from suicide gene,gene silencing,tumor suppress gene,immune gene and anti-angiogenesis gene. Suicide gene therapy system include: HSV-tk GCV system,H19 RNA,h TERT,etc. HSV-tk GCV system is one of the most studied suicide gene therapy system. TK gene is drug sensitivity gene and tumor cells will be kill by GCV or ACV after transfect with TK gene.RNA interference is a major mode of gene silencing therapy. The growth of tumor was inhibited obviously when silent tumor related genes( IDO2,DUSP6,IGF1 R,ORAOV1,etc.). Activation or overexpression of tumor suppress genes can also suppress tumor growth,such as p53 and PTEN gene. Cytokines or costimulatory molecules were used to activate immune functions of body to kill tumor cells in immune gene therapy. Common immunologic effector cells were TIL,CTL,LAK,NK,etc. and target genes were TNFIL,CSF,IFN,CF,etc. Anti-angiogenesis gene by suppressing anti-angiogenesis in tumors for stopping tumor growth and metastasis. VEGF-Trap,PEDF,ES can significantly inhibit tumor growth by transfected with adenovirus. The problems such as specificity,safety and targeting still exist in current cancer gene therapy.
引文
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