GENETHERAPYShifaCollegeofMedicineClassof基因疗法希法医学院级实用.pptxVIP

会计学1GENETHERAPYShifaCollegeofMedicineClassof基因疗法希法医学院级实用 GENE THERAPY Any procedure intended to treat or alleviate disease by genetically modifying the cells of a patient第1页/共25页 GENE THERAPY Delivery mechanismEx vivoIn vivo Type of cells modifiedGerm-line cellsSomatic cells Mechanism of modificationGene augmentation/supplementationGene replacementTargeted inhibition of gene expressionTargeted killing of specific cells第2页/共25页 DELIVERY MECHANISMSin vivo genetic material transferred directly into cells within a patientex vivo cells are removed from the patient, genetically modified and transplanted back into the patient第3页/共25页 (In vivo)(ex vivo)DELIVERY MECHANISMS第4页/共25页 Germ-line gene therapyModification of gametes, zygote or early embryoPermanent and transmissibleBanned due to ethical issues Somatic cell gene therapyModification of somatic cells, tissues etc Confined to the patientTYPES OF CELLS MODIFIED第5页/共25页 Targeted at disorders where pathogenesis is reversible Recessive disorders are more amendable to treatment than dominant disorders Gain-of-function mutations are untreatable by GATMechanism of modification1. Gene augmentation第6页/共25页 Mechanism of modification2. Gene replacement第7页/共25页 Mechanism of modification 3. Targeted killing of specific cells第8页/共25页 Mechanism of modification4.Targeted inhibition of gene expressionGain-of-function diseases where mutant gene is producing a harmful protein第9页/共25页 Amenability to gene therapy Mode of inheritanceIdentity of molecular defectNature of mutation productAccessibility of target cells and amenability to cell cultureSize of coding DNAControl of gene expression 第10页/共25页 Gene transferCloned geneIntegrated geneEpisomal geneCell division第11页/共25页 Vectors in useViralRetro-Adeno-Adeno-associated-Herpes simplex- Non-viralNaked DNA/Plasmidliposomes第12页/共25页 Retrovirusescreate cDNA copies from the viral RNA genome integrate into the human genomeMaximum insert size 7-7.5 kbPreexisting host immunity u