医学遗传学课件：chapter 18 treatment.pptVIP

Gene Therapy Trials Ashanti de Silva Ashanti was the first patient to be treated with gene therapy. Injections repeated 7 times in first 10.5 months ADA: 1% 25% Gene Therapy Trials Hemophilia B Xue Jinglun 薛京伦(Fudan university) 1991, Retrovirus Skin fibroblast Factor IX: 5% 2003, rAAV2-hF.IX 肿瘤的基因治疗 对宿主细胞的修饰 对肿瘤细胞的修饰 Gene therapy of tumors 对宿主细胞的修饰 将药物抗性基因转移至造血前体细胞以降低治疗药物对骨髓的毒性,可以用高剂量的药物杀伤肿瘤细胞而不破坏骨髓细胞。 导入细胞因子基因而扩大抗肿瘤效应。 MDR Gene 多药耐药基因疗法 ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? Multidrug-Resistance Gene Cytokine 细胞因子疗法 1984-1987, lymphokine activated killer cell (LAK) 1986, tumor infiltrate lymphocytes (TIL)/IL-2 1991, tumor necrosis factor (TNF) Vascular endothelial cell growth factor (VEGF) 对肿瘤细胞的修饰 改正肿瘤细胞的基因突变，降低其生长率，诱导肿瘤消退。 导入酶药物前体（pro-drug），形成肿瘤特异的敏感性。 导入目的基因以增强肿瘤的免疫原性，从而被机体的免疫系统所识别。 Tumor Suppressor Gene 抑癌基因疗法 Anti-oncogene Gene replacement therapy A method for replacing a mutated or missing gene (usually a tumor suppressor gene) that serves to keep cell growth and division under control with a normal copy of that gene. Rb, p53, p16, p21, p27 Gene Replacement Therapy Gene Replacement Therapy Apoptosis Suicide Gene “自杀基因”疗法 A gene that transforms a nontoxic form of a drug (pro-drug) into a toxic substance. herpes simplex virus thymidine kinase gene (HSV1TK) Suicide Gene By-stander effect The toxic substance (transform from pro-drug) diffuses out into wide surrounding area and kills other tumour cells. 1992, HSV-TK/GCV (brain tumor) Suicide Gene By-stander effect Suicide Gene By-stander effect ? Suicide Gene By-stander effect ? Suicide Gene By-stander effect Antisense Nucleic Acid 反义寡核苷酸技术 A nucleic acid molecular with a nucleotide sequence complementary to a specified mRNA. Antisense RNA expression vector Direct injection of antisense RNA/DNA Antisense RNA delivered by liposome Others 5′???C A U G???3′?????mRNA3′???G U A C???5′?????Antisense RNA 　 RNA interference （RNAi） RNA干扰 RNA干扰是双链 RNA(do