药物发现和发展专家讲座

DrugDiscovery

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Development药物发现和发展专家讲座第1页IntroductionInthepastmostdrugshavebeendiscoveredeitherbyidentifyingtheactiveingredientfromtraditionalremediesorbyserendipitousdiscovery.Butnowweknowdiseasesarecontrolledatmolecularandphysiologicallevel.Alsoshapeofanmoleculeatatomicleveliswellunderstood.InformationofHumanGenome药物发现和发展专家讲座第2页HistoryofDrugDiscovery:Pre1919HerbalDrugsSerendiptiousdiscoveries1920s,30sVitaminsVaccines1940sAntibioticEraR&DBoostduetoWW21950sNewtechnology,DiscoveryofDNA1960sBreakthroughinEtiology1970sRiseofBiotechnologyUseofIT1980sCommercializationofDrugDiscoveryCombinatorialChemistry1990sRoboticsAutomation药物发现和发展专家讲座第3页Registration:TheMinistryofhealth&FamilyWelfareandtheMinistryofChemicals&FertilizershavemajorroleinregulationofIPM.NDAmustbesubmittedtoDCGIPhaseIIIstudyreportedtoCDL,KolkataPackageinsertedapprovedbyDCIMarketingapprovalfromFDA药物发现和发展专家讲座第4页~$800Mspenttobringanewdrugtomarket.$127BillionspentonPharmaR&DinShareofCROsinresearchoperationsis27%WorldCROmarketis16.3B(Indianshare$500M)MarketScenerio:药物发现和发展专家讲座第5页TopCROs(ByRevenue)ContractResearchOrganizationsRevenueQuintiles$2.5BillionPharmaceuticalProductDevelopment$1.8BillionCovance$1.4BillionCharlesRiverLaboratories$1.2BillionParexel$930MillionIcon$887MillionKendle$590MillionPharmanet$470MillionPRAInternational$410Million4GPharmacovigilance$391Million药物发现和发展专家讲座第6页TopCROs(India)ContractResearchOrganizationsLocationActimusBiosciencesHyderabadAdvinusTherapeuticsBangaloreAurigeneDiscoverytechnologiesBangaloreChembiotekKolkataGVKBiosciencesHyderabadJubilantOrganosysBangaloreRanbaxyLifeSciencesMumbaiRelianceLifeSciencesMumbaiSuvenLifeSciencesHyderabadSyngeneBangalore药物发现和发展专家讲座第7页MostvaluableR&DProjectsRankProductCompanyPhasePharmacologicalclassToday'sNPV($mn)1DegludecNovoNordiskPhaseIIIInsulin5,8072TofacitinibPfizerPhaseIIIJAK-3inhibitor4,9533BG-12BiogenIdecPhaseIIIFumarate4,6664IncivekJ&JPhaseIVHepCproteaseinhibitor4,3325RelovairTheravancePhaseIIICorticosteroid4,2416DRCysteamineUndisclosedPhaseIIILysosomaltransportmodulator4,1557AMR101UndisclosedPhaseIIIOmega-3fattyacid4,0528EliquisBristolMyersSquibbPhaseIVFactorXainhibitor3,8369EliquisPfizerPhaseIVFactorXainhibitor3,59210BexsseroNovartisPhaseIVMeningococcalBvaccine3,250药物发现和发展专家讲座第8页TopCompaniesbyR&DExpense:Sr.No.CompanyR&Dspend($bn),1Novartis7.92Merck&Co8.13Roche7.84GlaxoSmithKline5.75Sanofi5.86Pfizer9.17Johnson&Johnson4.58EliLilly4.79AstraZeneca4.210Takeda3.411Bayer2.312Bristol-MyersSquibb3.313BoehringerIngelheim3.114Amgen2.815NovoNordisk1.7药物发现和发展专家讲座第9页DrugDevelopmentCostBreak-upR&DFunction%Discovery/BasicResearchSynthesis&Extraction10.0BiologicalScreening&testing14.2PreclinicalTestingToxicology&Safetytesting4.5PharmaceuticalDosageFormulation7.3ClinicalTrialsPhaseI,II,III29.1PhaseIV11.7Manufacturing&QC8.3IND&NDA4.1Bioavailability1.8Others9.0Total100.0药物发现和发展专家讲座第10页10,000COMPOUNDS250COMPOUNDS5COMPOUNDS1FDAAPPROVEDDRUG~6.5YEARS~7YEARS~1.5YEARSDRUGDISCOVERYPRECLINICALCLINICALTRIALSFDAREVIEWDrugDiscovery&Development-Timeline药物发现和发展专家讲座第11页DrugDiscoveryDrugsDiscoverymethods:RandomScreeningMolecularManipulationMolecularDesigningDrugMetabolitesSerendipity药物发现和发展专家讲座第12页TargetSelectionCellularandGeneticTargetsGenomicsProteomicsBioinformaticsLeadDiscoverySynthesisandIsolationCombinatorialChemistryAssaydevelopmentHigh-ThroughputScreeningMedicinalChemistryLibraryDevelopmentSARStudiesInSilicoScreeningChemicalSynthesisInVitroStudiesDrugAffinityandSelectivityCellDiseaseModelsMOALeadCandidateRefinementInVivoStudiesAnimalmodelsofDiseaseStatesBehaviouralStudiesFunctionalImagingEx-VivoStudiesClinicalTrialsandTherapeutics药物发现和发展专家讲座第13页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsTargetSelectionTargetselectionindrugdiscoveryisdefinedasthedecisiontofocusonfindinganagentwithaparticularbiologicalactionthatisanticipatedtohavetherapeuticutility—isinfluencedbyacomplexbalanceofscientific,medicalandstrategicconsiderations.Targetidentification:toidentifymoleculartargetsthatareinvolvedindiseaseprogression.Targetvalidation:toprovethatmanipulatingthemoleculartargetcanprovidetherapeuticbenefitforpatients.药物发现和发展专家讲座第14页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsTargetSelectionBiochemicalClassesofDrugTargetsG-proteincoupledreceptors-45%enzymes-28%hormonesandfactors-11%ionchannels-5%nuclearreceptors-2%TechniquesforTargetIdentification药物发现和发展专家讲座第15页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsCellular&GeneticTargets:Involvestheidentificationofthefunctionofapotentialtherapeuticdrugtargetanditsroleinthediseaseprocess.Forsmall-moleculedrugs,thisstepintheprocessinvolvesidentificationofthetargetreceptorsorenzymeswhereasforsomebiologicapproachesthefocusisatthegeneortranscriptionlevel.Drugsusuallyactoneithercellularorgeneticchemicalsinthebody,knownastargets,whicharebelievedtobeassociatedwithdisease.药物发现和发展专家讲座第16页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsCellular&GeneticTargets:Scientistsuseavarietyoftechniquestoidentifyandisolateindividualtargetstolearnmoreabouttheirfunctionsandhowtheyinfluencedisease.Compoundsarethenidentifiedthathavevariousinteractionswiththedrugtargetsthatmightbehelpfulintreatmentofaspecificdisease.药物发现和发展专家讲座第17页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsGenomics:Thestudyofgenesandtheirfunction.Genomicsaimstounderstandthestructureofthegenome,includingthemappinggenesandsequencingtheDNA.Seekstoexploitthefindingsfromthesequencingofthehumanandothergenomestofindnewdrugtargets.HumanGenomeconsistsofasequenceofaround3billionnucleotides(theACGTbases)whichinturnprobablyencode35,000–50,000genes.

药物发现和发展专家讲座第18页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsGenomics:Drew’sestimatesthatthenumberofgenesimplicatedindisease,boththoseduetodefectsinsinglegenesandthosearisingfromcombinationsofgenes,isabout1,000Basedon5or10linkedproteinspergene,heproposesthatthenumberofpotentialdrugtargetsmayliebetween5,000and10,000.SingleNucleotidePolymorphism(SNP)libraries:areusedtocomparethegenomesfrombothhealthyandsickpeopleandtoidentifywheretheirgenomesvary.药物发现和发展专家讲座第19页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsProteomics:Itisthestudyoftheproteome,thecompletesetofproteinsproducedbyaspecies,usingthetechnologiesoflarge–scaleproteinseparationandidentification.Itisbecomingincreasinglyevidentthatthecomplexityofbiologicalsystemsliesattheleveloftheproteins,andthatgenomicsalonewillnotsufficetounderstandthesesystems.

Itisalsoattheproteinlevelthatdiseaseprocessesbecomemanifest,andatwhichmost(91%)drugsact.

Therefore,theanalysisofproteins(includingprotein-protein,protein-nucleicacid,andproteinligandinteractions)willbeutmostimportancetotargetdiscovery.药物发现和发展专家讲座第20页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsProteomics:Proteomicsisthesystematichigh-throughputseparationandcharacterizationofproteinswithinbiologicalsystems.Targetidentificationwithproteomicsisperformedbycomparingtheproteinexpressionlevelsinnormalanddiseasedtissues.2DPAGEisusedtoseparatetheproteins,whicharesubsequentlyidentifiedandfullycharacterizedwithLC-MS/MS.药物发现和发展专家讲座第21页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsBioinformatics:Bioinformaticsisabranchofmolecularbiologythatinvolvesextensiveanalysisofbiologicaldatausingcomputers,forthepurposeofenhancingbiologicalresearch.Itplaysakeyroleinvariousstagesofthedrugdiscoveryprocessincludingtargetidentificationcomputerscreeningofchemicalcompoundsandpharmacogenomics

药物发现和发展专家讲座第22页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsCellular&GeneticTargetsGenomicsProteomicsBioinformaticsBioinformatics:Bioinformaticsmethodsareusedtotransformtherawsequenceintomeaningfulinformation(eg.genesandtheirencodedproteins)andtocomparewholegenomes(diseasevs.not).

Cancomparetheentiregenomeofpathogenicandnon-pathogenicstrainsofamicrobeandidentifygenes/proteinsassociatedwithpathogenism

Usinggeneexpressionmicroarraysandgenechiptechnologies,asingledevicecanbeusedtoevaluateandcomparetheexpressionofupto0genesofhealthyanddiseasedindividualsatonce药物发现和发展专家讲座第23页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsSynthesisandIsolationCombinatorialChemistryAssayDevelopmentHighThroughputScreeningLeadDiscovery:IdentificationofsmallmoleculemodulatorsofproteinfunctionTheprocessoftransformingtheseintohigh-contentleadseries.药物发现和发展专家讲座第24页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsSynthesisandIsolationCombinatorialChemistryAssayDevelopmentHighThroughputScreeningSynthesisandIsolation:SeparationofmixtureSeparationofimpuritiesInvitrochemicalsynthesisBiosyntheticintermediate药物发现和发展专家讲座第25页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsSynthesisandIsolationCombinatorialChemistryAssayDevelopmentHighThroughputScreeningCombinatorialChemistry:Rapidsynthesisoforcomputersimulationoflargeno.ofdifferentbutstructurallyrelatedmoleculesSearchnewleadsOptimizationoftargetaffinity&selectivity.ADMEpropertiesReducetoxicityandeliminatesideeffects药物发现和发展专家讲座第26页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsSynthesisandIsolationCombinatorialChemistryAssayDevelopmentHighThroughputScreeningAssayDevelopmentUsedformeasuringtheactivityofadrug.Discriminatebetweencompounds.Evaluate:Expressedproteintargets.Enzyme/substrateinteractions.药物发现和发展专家讲座第27页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsSynthesisandIsolationCombinatorialChemistryAssayDevelopmentHighThroughputScreeningHighthroughputscreening:Screeningofdrugtargetagainstselectionofchemicals.Identificationofhighlytargetspecificcompounds.药物发现和发展专家讲座第28页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsSynthesisandIsolationCombinatorialChemistryAssayDevelopmentHighThroughputScreeningHighthroughputscreening:药物发现和发展专家讲座第29页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsLibraryDevelopmentSARStudiesInSilicoScreeningChemicalSynthesisMedicinalChemistry:It’sadisciplineattheintersectionofsyntheticorganicchemistryandparmacology.Focusesonsmallorganicmolecules(andnotonbiologicsandinorganiccompounds)UsedinDrugdiscovery(hits)Leadoptimization(hittolead)Processchemistryanddevelopment药物发现和发展专家讲座第30页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsLibraryDevelopmentSARStudiesInSilicoScreeningChemicalSynthesisLibraryDevelopment:Collectionofstoredchemicalsalongwithassociateddatabase.AssistsinHighThroughputScreeningHelpsinscreeningofdrugtarget(hit)Basedonorganicchemistry药物发现和发展专家讲座第31页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsLibraryDevelopmentSARStudiesInSilicoScreeningChemicalSynthesisSARStudies:HelpsidentifypharmacophoreThepharmacophoreistheprecisesectionofthemoleculethatisresponsibleforbiologicalactivityEnablestopreparemoreactivecompoundAlloweliminationofexcessivefunctionality药物发现和发展专家讲座第32页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsLibraryDevelopmentSARStudiesInSilicoScreeningChemicalSynthesisSARStudies:MorphineMolecule药物发现和发展专家讲座第33页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsLibraryDevelopmentSARStudiesInSilicoScreeningChemicalSynthesisInsilicoscreening:ComputersimulatedscreeningofchemicalsHelpsinfindingstructuresthataremostlikelytobindtodrugtarget.FilterenormousChemicalspaceEconomicthanHTS药物发现和发展专家讲座第34页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsLibraryDevelopmentSARStudiesInSilicoScreeningChemicalSynthesisChemicalSynthesis:Involveproductionofleadcompoundinsuitablequantityandqualitytoallowlargescaleanimalandeventual,extensivehumanclinicaltrialsOptimizationofchemicalrouteforbulkindustrialproduction.Suitabledrugformulation药物发现和发展专家讲座第35页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsDrugAffinityandSelectivityCellDiseaseModelsMOALeadCandidateRefinementInVitroStudies:(Inglass)studiesusingcomponentoforganismi.e.testtubeexperimentsExamples-CellsderivedfrommulticellularorganismsSubcellularcomponents(Ribosomes,mitochondria)Cellular/subcellularextracts(wheatgerm,reticulocyteextract)Purifiedmolecules(DNA,RNA)药物发现和发展专家讲座第36页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsDrugAffinityandSelectivityCellDiseaseModelsMOALeadCandidateRefinementInVitroStudies:Advantages:Studiescanbecompletedinshortperiodoftime.Reducesriskinpostclinicaltrials

permitsanenormouslevelofsimplificationofthesysteminvestigatorcanfocusonasmallnumberofcomponents药物发现和发展专家讲座第37页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsDrugAffinityandSelectivityCellDiseaseModelsMOALeadCandidateRefinementDrugaffinityandselectivityDrugaffinity

istheabilityofdrugtobindtoitsbiologicaltarget(receptor,enzyme,transportsystem,etc.)Selectivity-Drugshouldbindtospecificreceptorsiteonthecell(eg.Aspirin)药物发现和发展专家讲座第38页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsDrugAffinityandSelectivityCellDiseaseModelsMOALeadCandidateRefinementIsogenichumandiseasemodels-areafamilyofcellsthatareselectedorengineeredtoaccuratelymodelthegeneticsofaspecificpatientpopulation,invitroStemcelldiseasemodels-AdultorembryonicstemcellscarryingorinducedtocarrydefectivegenescanbeinvestigatedinvitrotounderstandlatentmolecularmechanismsanddiseasecharacteristicsCelldiseasemodels药物发现和发展专家讲座第39页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsDrugAffinityandSelectivityCellDiseaseModelsMOALeadCandidateRefinementOptimizingchemicalhitsforclinicaltrialiscommonlyreferredtoasleadoptimization

TherefinementinstructureisnecessaryinordertoimprovePotencyOralAvailabilitySelectivitypharmacokineticpropertiessafety(ADMEproperties)LeadCandidaterefinement药物发现和发展专家讲座第40页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsAnimalmodelsofDiseaseStatesBehaviouralStudiesFunctionalImagingEx-VivoStudiesInvivostudiesItsexperimentationusingawhole,livingorganism.Givesinformationabout,MetabolicprofileToxicologyDruginteraction药物发现和发展专家讲座第41页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsAnimalmodelsofDiseaseStatesBehaviouralStudiesFunctionalImagingEx-VivoStudiesAnimalmodelsofdiseasestatesTestconditionsinvolvinginduceddiseaseorinjurysimilartohumanconditions.Mustbeequivalentinmechanismofcause.Canpredicthumantoxicityin71%ofthecases.Eg.SCIDmice-HIV NOD

mice-Diabetes

Daniorerio-Genefunction药物发现和发展专家讲座第42页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsAnimalmodelsofDiseaseStatesBehaviouralStudiesFunctionalImagingEx-VivoStudiesBehaviouralStudiesToolstoinvestigatebehaviouralresultsofdrugs.Usedtoobservedepressionandmentaldisorders.Howeverselfesteemandsuicidalityarehardtoinduce.Example:Despairbased-Forcedswimming/TailsuspensionRewardbasedAnxietyBased药物发现和发展专家讲座第43页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsAnimalmodelsofDiseaseStatesBehaviouralStudiesFunctionalImagingEx-VivoStudiesFunctionalImaging:Methodofdetectingormeasuringchangesinmetabolism,bloodflow,regionalchemicalcomposition,andabsorption.Tracersorprobesused.ModalitiesUsed-MRICT-Scan药物发现和发展专家讲座第44页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsAnimalmodelsofDiseaseStatesBehaviouralStudiesFunctionalImagingEx-VivoStudiesEx-VivoStudies:Experimentationontissueinanartificialenvironmentoutsidetheorganismwiththeminimumalterationofnaturalconditions.Countersethicalissues.Examples:MeasurementoftissuepropertiesRealisticmodelsforsurgery药物发现和发展专家讲座第45页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsPhase-IPhase-IIPhase-IIIPhase-IVClinicaltrials:Setofproceduresinmedicalresearchanddrugdevelopmenttostudythesafetyandefficacyofnewdrug.Essentialtogetmarketingapprovalfromregulatoryauthorities.Mayrequireupto7years.药物发现和发展专家讲座第46页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsPhase-IPhase-IIPhase-IIIPhase-IVPhase0:Recent

designation,alsoknownashumanmicro-dosingstudies.Firstinhumantrials,conductedtostudyexploratoryinvestigationalnewdrug.Designedtotospeedupthedevelopmentofpromisingdrugs.Concernedwith-Preliminarydataonthedrug’spharmacodynamicsandpharmacokineticsEfficacyofpre-clinicalstudies.药物发现和发展专家讲座第47页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsPhase-IPhase-IIPhase-IIIPhase-IVPhaseI:ClinicalPharmacologicEvaluationFirststageoftestinginhumansubjects.20-50HealthyVolunteersConcernedWith:HumanToxicity.ToleratedDosageRangePharma-cology/dynamics药物发现和发展专家讲座第48页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsPhase-IPhase-IIPhase-IIIPhase-IVPhaseI:TypesofPhase-ITrialsSAD(SingleAscendingDose)MAD(MultipleAscendingDose)Foodeffect药物发现和发展专家讲座第49页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsPhase-IPhase-IIPhase-IIIPhase-IVPhaseII:ControlledClinicalEvaluation.50-300PatientsControlledSingleBlindTechniqueConcernedWith:SafetyEfficacyDrugToxicityDrugInteraction药物发现和发展专家讲座第50页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsPhase-IPhase-IIPhase-IIIPhase-IVPhaseIII:ExtendedClinicalTrials.Mostexpensive&timeconsuming.250-1000Patients.ControlledDoubleBlindTechnique.ConcernedWith:Safety,EfficacyComparisonwithotherDrugsPackageInsert药物发现和发展专家讲座第51页TargetSelection LeadDiscoveryMedicinalChemistryInVitroStudiesInVivoStudiesClinicalTrialsPhase-IPhase-IIPhase-IIIPhase-IVPhaseIV:PostMarketingSurveillance.Designedtodetectanyrareorlong-termadverseeffects.AdverseDrugReactionMonitoring.Pharmacovigilance.药物发现和发展专家讲座第52页10,000COMPOUNDS250COMPOUNDS5COMPOUNDS1FDAAPPROVEDDRUG~6.5YEARS~7YEARS~1.5YEARSDRUGDISCOVERYPRECLINICALCLINICALTRIALSFDAREVIEWDrugDiscovery&Development-Timeline药物发现和发展专家讲座第53页GeneTherapyTechniqueforcorrectingdefectivegenes.Itistheprocessofinsertinggenesintocellstotreatdiseases.Genetherapyisusedtocorrectadeficientphenotype.药物发现和发展专家讲座第54页GeneTherapy-ApproachesGermlineGeneTherapySpermoreggs,aremodifiedbytheintroductionoffunctionalgenes,whichareintegratedintotheirgenomes.Change