GENETHERAPYShifaCollegeofMedicineClassof基因疗法希法医学院级实用PPT学习教案

1、会计学1GENETHERAPYShifaCollegeofMedicineClassof基因疗法希法医学院级实用基因疗法希法医学院级实用第1页/共25页onnGene replacementnTargeted inhibition of gene expressionnTargeted killing of specific cells第2页/共25页in vivo genetic material transferred directly into cells within a patientex vivo cells are removed from the patient, geneti

2、cally modified and transplanted back into the patient第3页/共25页(In vivo)(ex vivo)DELIVERY MECHANISMSDELIVERY MECHANISMS第4页/共25页cells, tissues etc nConfined to the patient第5页/共25页 Targeted at disorders where pathogenesis is reversible Recessive disorders are more amendable to treatment than dominant di

3、sorders Gain-of-function mutations are untreatable by GATMechanism of modificationMechanism of modification1. Gene augmentation1. Gene augmentation第6页/共25页Mechanism of modificationMechanism of modification2. Gene replacement2. Gene replacement第7页/共25页第8页/共25页Mechanism of modificationMechanism of mod

4、ification4.4.Targeted inhibition of gene expressionGain-of-function diseases where mutant gene is producing a harmful protein第9页/共25页第10页/共25页Cloned geneIntegrated geneEpisomal geneCell division第11页/共25页第12页/共25页create cDNA copies from the viral RNA genome integrate into the human genomeMaximum inse

5、rt size 7-7.5 kbPreexisting host immunity unlikelyCan only transduce dividing cellsMay cause insertional mutagenesis第13页/共25页RetrovirusesRetrovirusesLentiviruses (e.g HIV)Maximum insert size 7-7.5 kbCan transduce non-dividing cellsMay cause insertional mutagenesis第14页/共25页第15页/共25页small, single stra

6、nded DNA virusesproductive infection only with co-infection by another virusinsert genetic material at a specific point on chromosome 19Low information capacity- 4.0 KbAdeno-associatedAdeno-associated VirusesViruses第16页/共25页Complex ds DNAEstablish life long latent infections as non-integrated extra chromosomal elementsinformation capacity 30 KbHerpes simplex VirusesHerpes simplex Viruses第17页/共25页第18页/共25页第19页/共25页第20页/共25页第21页/共25页第22页