molbi思osp04pres01.ppt

Manufactured Protein Therapeutics制造具有疗效的蛋白 Crude Protein粗蛋白 Purify纯化 Quality Control品质控制 Frequent Administration To patient治疗应用 i.e., insulin胰岛素, growth hormone生长激素, EPO Culture of Organisms 生物培养表达 Advantages of DNA Vaccines Compared to Classical Vaccines相比较传统的疫苗，DNA生产的疫苗具有的优势 Simple to develop 研发比较容易 Inexpensive便宜 Effective: Protein presented in native form效果好：天然蛋白 Easy to transport and store运输和储存更容易 Safe: No risk of infection安全性：不会感染 Barriers to Gene Delivery in the Body基因在机体内表达需要克服的障碍 Lung Lung Heart Kidney Liver Gastrointestinal tract Urinary bladder Elimination by cells of RES网状内皮系统细胞的清除作用 Binding of serum proteins affects biodistribution血清蛋白的吸附作用影响生物分布 Target separated by a biological barrier (e.g. BBB or intestinal barrier) Low permeability of target tissues目标组织渗透压低 Degradation of nucleic acids核酸降解 Barriers to Gene Delivery in the Cell基因在细胞内表达需要克服的障碍 Uptake into a cell, usually through endocytosis (1)进入细胞，通常通过内吞作用 Accumulation in endosomes (2)在核内体内累积 Transport into lysosomes and degradation of DNA (2’)运输进入溶酶体，DNA降解 Escape from endosomes and/or lysosomes (3)从核内体或溶酶体逃脱 Vesicular transport inside the cell (4,4’)细胞内小泡运输 Transport into nucleus (5)运输进入细胞核 Avoidance of DNA purging and replication (6) Recycling (7) and transcytosis (7’)循环以及胞吞 1 2 2’ 3 3 Endosome Lysosome Nucleus 5 7’ 7 4’ 4’ 6 Site Specific Delivery Nuclear localization of wt human p53 in NIH3T3 cells The 7 requirements of a successful gene delivery system:成功的基因表达要需的7个条件 A practical gene delivery system must meet seven characteristics. It must be:基因表达必须具备的7个条件： Efficient in introducing the genes to recipient cells 将基因导入受体细胞 Capable of achieving long term expression or short term expression (depending on use)能够长期或者短期表达，而不是一时半会的某一时刻的 Flexible with respect to the target tissues it can deliver to与目标组织具有高度的兼容性 Harmless to the patient对病人无害 Able to handle a wide range of therapeutic genes能够处理很多类型的治疗性基因 Able to demonstrate a dose-response relationship具有剂量反应关系 Supplied in a form familiar and com