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1、 Chapter 13 Gene Therapy 13.1 Basic strategies for gene therapy A new manner of clinical treatment that transfers certain genetic material into the patients cells and ensure it work in vivo to administrate the disease is called gene therapy.Concept of gene therapy 13.1 Basic strategies for 13.1 Basi
2、c strategies for gene therapygene therapy （1）Gene replacement（2）Gene augmentation（3）Gene interference（4）Suicide gene therapy（5）Gene immunotherapy（1)Gene replacement Definition:The introduction of specific target genes into specific cells,through the site-specific recombination,i.e.,the introduction
3、of normal gene to displace the original defective gene.Objective:To correct the abnormal sequence of defective genes.accurate in situ repair of defective sites of defective genes and does not involve any changes in the genome.Conditions of directional integration:vectors of transduction genes have t
4、he same sequence as genomic DNA.The vector with the target gene can find the site of homologous recombination and exchange some gene sequences,thus the treatment strategy works.Also known as gene targeting Gene homologous recombination Gene homologous recombination technologytechnology Defect genes
5、Normal gene Recombinant vector Normal gene Positioning and reorganization technology Chromosome Insertion Gene Homologous Recombination Technology Principle Animation（2）Gene augmentation Definition:Target cells express genes that are introduced to compensate for the innate gene dysfunction.Type：A.Th
6、e corresponding normal genes are introduced into the cells with defective genes.The defective genes in the cells are not removed,however,its function is compensated by the expressional products of the normal genes;B.The target gene introduced does not originally expressed in the cells.Definition:Use
7、 specific ways to inhibit the expression of a gene,or by destroying the structure of a gene so that it can not be expressed appropriately.e.g.antisense nucleic acids,ribozymes or interference RNA techniques,etc.（3）Gene interference One of the main methods of gene therapy for malignant tumors.Princip
8、le:The suicide gene is introduced into the host cell.The enzyme encoded by this gene can transform the nontoxic drug(prodrug)into a cytotoxic metabolite and induce the target cell to commit suicide”,thus to eliminate tumor cells.（4）Suicide gene therapy Mechanism of the Suicide Gene A.TK/GCV：herpes s
9、implex virus(HSV)type I thymidine kinase(TK)gene encodes thymidine kinase,specifically transforming the nontoxic nucleoside analogue ganciclovir(GCV)into the toxic triphosphate nucleoside GCV,which inhibits DNA polymerase activity and leading to cell death.The suicide gene system B.The escherichia c
10、oli cytosine deaminase(CD)gene,which converts nontoxic 5-fluorocytosine(5-FC)into toxic product 5-fluorouracil(5-FU)in cells.The suicide gene system Bystander effect：not only the tumor cells that hide the introduced suicide gene“but also those adjacent to it or even in distance which were unsuccessf
11、ully transduced were killed after prodrug administration.Enable suicide gene therapy an enhanced tumor-killing effect.Bystander effect(5)Gene immunotherapy By introducing anti-cancer immune-enhancing cytokines or MHC genes into tumor tissues to increase the anti-cancer immune response in the tumor m
12、icroenvironment.（1）Gene-modified vaccine therapy for tumor cells （2）Genetic modified TIL adoptive immunotherapy （3）Immune-enhancing gene therapy （4）Gene therapy to modify tumor immunogenicity in situ Review：1.What are the basic strategies for gene therapy?2.Illustrate the application of gene intervention technology in gene therapy.