目的　应用ADP核糖化细菌毒素基因探讨对CEA阳性大肠癌的组织特异性基因疗法。方法　从铜绿假单孢菌基因组DNA和质粒 pET15b DT中分别克隆假单孢菌外毒素Ⅱ +Ⅲ区基因 (PEA)和白喉外毒素A链 (DTA)基因 ,引入Kozak序列 ,终止信号和酶切位点 ,测序后置于CEA启动子调控下克隆到逆转录病毒载体中。研究体外表达和裸鼠体内抗肿瘤能力。结果　体外荧光素酶共转染试验证明CEA启动子调控的毒性基因在CEA阳性大肠癌细胞中可以特异抑制报告基因表达。在裸鼠模型中 ,构建物与脂质体共转染肿瘤瘤体内可以使人大肠癌选择性消退 ,而对CEA阴性的肾癌模型无显著作用。结论　ADP核糖化毒性基因作为治疗基因适合于肿瘤组织特异性基因治疗 Objective To investigate the tissue-specific gene therapy for CEA-positive colorectal cancer using ADP ribosylating bacterial toxin gene. Methods Pseudomonas exotoxin II + III gene (PEA) and diphtheria exotoxin A chain (DTA) genes were cloned from Pseudomonas aeruginosa genomic DNA and plasmid pET15b DT, respectively, and the Kozak sequence was introduced to terminate the signal and cut the enzyme. Sites, after sequencing, were cloned into retroviral vectors under the control of the CEA promoter. To study in vitro expression and anti-tumor ability in nude mice. Results In vitro luciferase co-transfection experiments demonstrated that CEA promoter-regulated virulence genes can specifically inhibit reporter gene expression in CEA-positive colorectal cancer cells. In a nude mouse model, the co-transfection of the construct with liposomes in tumor tumours can cause selective regression of human colorectal cancer, while it has no significant effect on CEA-negative kidney cancer models. Conclusion ADP ribosylating virulence gene as therapeutic gene is suitable for tumor tissue-specific gene therapy