肿瘤基因治疗的靶向策略(英文)  

Targeting Strategies in Cancer Gene Therapy

作　　者：王晋慧[1] 刘新垣[1] 

机构地区：[1]中国科学院上海生命科学研究院生物化学与细胞生物学研究所,上海200031

出　　处：《生物化学与生物物理学报》2003年第4期311-316,共6页

基　　金：中国科学院"九五"重大项目 (No .KSCX2 3 0 6);国家自然科学基金资助项目 (No.3 0 12 0 160 82 3 );国家高技术研究发展计划 (863计划 )资助项目 (No .2 0 0 1AA2 170 3 1)~~

摘　　要：对肿瘤组织的靶向性可以提高基因治疗的效果 ,避免对正常组织的损伤 ,并且能降低作为载体的微生物对机体的危害。对于瘤内注射的给药方法 ,靶向性似乎显得不是特别重要 ,但是如果要系统给药 ,靶向性是很关键的一个问题。靶向基因治疗肿瘤可以通过靶向基因导入和靶向基因表达来实现。近年来 ,在靶向基因导入方面的研究有很多进展 ,例如 ,用双亲性的桥连分子协助腺病毒和逆转录病毒靶向转导 ;在各种病毒载体的衣壳蛋白中插入靶向性的小肽或较大的多肽靶向结构域 ;增殖病毒作为一种很有前途的抗肿瘤制剂可有效地靶向杀伤肿瘤细胞。受体介导的DNA或DNA 脂质体复合物的靶向系统和其他一些靶向性的有疗效的载体 ,如细菌 ,也处于研究中。其中的一些载体已经进入临床实验。为了实现基因的靶向可调控表达 ,组织或肿瘤特异性的启动子和人工合成的可调控表达系统被用来调控治疗基因的表达。反义核酸、核酶以及脱氧核酶 (DNAzyme)被用来靶向抑制与肿瘤发生密切相关基因的表达。Targeting to the tumor tissues can improve the therapeutic effect of gene transfer by preventing damage of healthy tissues and decreasing the risk of germ line transduction. Although targeting seems not important for intratumoral gene delivery, it becomes crucial when systemic gene transfer is performed. Targeted gene therapy of malignancies can be achieved through targeted gene delivery or targeted gene transcription. Recent advances in targeted delivery include the successful use of bifunctional crosslinkers to target adenoviral and retroviral vectors, inserting short targeting peptides and larger polypeptide-binding domains into the coat proteins of a number of different viral vectors, and replication-competent vectors which have been shown to be promise as anti-cancer agents. Some other non-viral therapeutic agents, including receptor-mediated DNA or liposome-DNA complex, and bacteria vehicles have also been developed. Some of these delivery systems are currently in clinical trials. For targeted and regulable gene transcription, tissue or tumor specific promoters and some manual regulatory systems are used to regulate therapeutic gene expression. Antisense oligonucleotides, some ribozyme and DNAzyme molecules are developed to inactivate genes that are essential to the development of many tumors.

关 键 词：肿瘤 基因治疗 靶向策略 靶向性 靶向基因 基因导入 基因表达 

分 类 号：R730.5[医药卫生—肿瘤] R394.8[医药卫生—临床医学]