RNAi湖南师范大学向双林院长课件1.ppt

* Gene therapy through bacteria delivered RNA interference Shuanglin Xiang Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University The Nobel Prize in Physiology or Medicine 2006 Andrew Z. Fire Craig C. Mello A natural existing mechanism of sequence-specific post-transcriptional gene silencing Double-stranded RNA enters a target cell, it is cleaved into short (~21nt) fragments by DICER RISC (RNA-induced silencing complex) separates these short interfering RNAs duplex (siRNA), a single strand RNA remains bound to the complex RISC-associated single strand RNA binds to homologous sequences in mRNA within the cytoplasm This binding triggers the cleavage of the target mRNA in the center of the matched sequence Cleaved mRNA is quickly degraded by cellular RNAses and can not be translated into protein Significance of the discovery of RNAi RNAi protects against viral infections RNAi secures genome stability by keeping mobile elements silent RNAi-like mechanisms repress protein synthesis and regulate the development of organisms RNAi-like mechanisms keep chromatin condensed and suppress transcription 5. RNAi offers a new experimental tool to repress genes specifically 6. RNAi might be a useful approach in future gene therapy Top 10 Cancers in China Male Lung cancer Gastric cancer Liver cancer Colorectal cancer Esophageal cancer Pancreatic cancer Bladder cancer Brain cancer Lymphoma Nasopharyngeal cancer Female Lung cancer Breast cancer Gastric cancer Colorectal cancer Liver cancer Esophageal cancer Ovarian cancer Cervical cancer Pancreatic cancer Brain cancer Delivery is a major problem for RNAi in vivo application (By Dr. Christopher P. Miller) Disease – FAP (Familial Adenomatous Polyposis) FAP is an autosomal, dominantly inherited disease that affects about 1 in 7000 individuals. Patients with FAP typically develop hundreds to thousands of colorectal tumors (c