昆医分生基因治疗不考试演示文稿.pptVIP

基因的整合途径 第三十页，共六十三页。 Exogenous genes that integrate into chromosomes can be stably transmitted to all daughter cells, unlike episomal (extrachromosomal) genes. The figure illustrates two possible fates of genes that have been transferred into nucleated cells. Gene therapy involving chromosomal integration of exogenous genes offers the possibility of continued stable expression of the inserted gene and a permanent cure, but carries certain risks, notably the possibility that one of the integration events may result in cancer . By contrast, episomal genes which do not integrate but replicate extrachromosomally (under the control of a vector origin of replication) may not segregate to all daughter cells during subsequent mitoses. As a result, this type of approach has been particularly applied in gene therapies where the target tissue consists of nondividing cells 。 第三十一页，共六十三页。 基因转导的载体 第三十二页，共六十三页。 转运载体要求： ① 能够高效转运治疗所需的一个或多个目的基因； ② 载体具有准确的靶向性，无免疫原性，易于生产、提纯； ③ 无致病性，对受者及环境无危害； ④ 使其所携带的基因能按要求准确表达。 理想载体目前仍无法得到。病毒为载体介导的基因转移具有靶向性好、效率高的特点，另外可利用细胞自身机制生产所需要的目的蛋白质，是目前进入临床前期研究的较为理想的载体之一。 第三十三页，共六十三页。 目前适用基因治疗的疾病 ⑴ 遗传性疾病，首选单基因缺陷症如镰状细胞病、甲型和乙型血友病、地中海贫血、ADA缺乏所致重症联合免疫缺陷病、嘌呤核苷磷酸化酶PNP缺乏症、遗传性α1-抗胰蛋白酶缺乏症、囊性纤维化等。 ⑵ 免疫缺乏病，如白细胞粘附分子缺陷病、TcR-CD3缺乏症。 ⑶ 肿瘤及恶性血液病，主要适用于基因突变者如膀胱癌、肺癌、乳腺癌、结肠癌、神经母细胞瘤、黑色素瘤、白血病等。 ⑷ 其他疾病如糖尿病、肌营养不良、高血压、某些精神病、AIDS、慢性活动型肝炎、心血管疾病等。 第三十四页，共六十三页。 单基因疾病的基因治疗 第三十五页，共六十三页。 Ex vivo gene augmentation therapy for adenosine deaminase (ADA) deficiency. Note that identification of suitably transformed cells is helped by having an appropriate selectable marker in the retrovirus vector, such as a neoR gene which confers resistance to the neomycin analog G418 . Following infection, the target cells can be cultured in a medium containing G418 to select for the presence of retroviral sequences, and then assayed by PCR for the presence of the inserted ADA gene. Suitable ADA+ cells can then be expanded in culture before being reintroduced into the patient. 第三十六页，共六十三页。 Examples of g