grant
Immunomodulation in AAV gene therapy
NIHUS FederalResearch GrantFY202519S Gamma Globulin7S Gamma GlobulinAAV vectorAAV-based vectorAcute Kidney FailureAcute Kidney InsufficiencyAcute Renal FailureAcute Renal InsufficiencyAddressAdoptionAdverse reactionsAnti-CD20 AntibodyAntibodiesAntibody ResponseAntiseraAutoimmune DiseasesB blood cellsB cellB cell receptorB cellsB-Cell ActivationB-Cell Antigen ReceptorB-CellsB-LymphocytesB-cellBacterial Gene ProductsBacterial Gene ProteinsBacterial ProteinsBloodBlood NeutrophilBlood Platelet TransfusionBlood Polymorphonuclear NeutrophilBlood Reticuloendothelial SystemBody TissuesC2B8 Monoclonal AntibodyCapsidCell BodyCell CommunicationCell Communication and SignalingCell CompartmentationCell CompartmentationsCell InteractionCell SignalingCell surfaceCell-to-Cell InteractionCellsCessation of lifeCirculationClinicClinicalClinical PathsClinical PathwaysClinical Treatment MoabClinical TrialsComplementComplement ActivationComplement ProteinsComplexConsensusDNA TherapyDanon DiseaseDeathDendritic CellsDevelopmentDiseaseDisorderDoseDrugsDucheneDuchenneDuchenne muscular dystrophyDuchenne-Griesinger syndromeEarly-Stage Clinical TrialsEllis-van Creveld (EvC) syndromeEmesisEngineeringEnzyme GeneEnzymesEsteroproteasesEventExposure toFDA approvedFeverFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryGasser's SyndromeGene DeliveryGene Transfer ClinicalGenetic InterventionGlycogen Storage Disease IIbGlycogen Storage Disease Type IIbGoalsGrafting ProcedureHalf-LifeHemodialysesHemodialysisHemolytic-Uremic SyndromeHepatotoxic effectHepatotoxicityHumanHumoral ImmunitiesIMiDIgGIgMImmuneImmune RegulatorsImmune SeraImmune memoryImmune modulatory therapeuticImmune responseImmunesImmunityImmunoglobulin GImmunoglobulin MImmunologic MemoryImmunological MemoryImmunomodulationImmunomodulatorsIn VitroIntracellular Communication and SignalingLifeLiverLiver ToxicityM mulattaM. mulattaMabTheraMacaca mulattaMacaca rhesusMapsMarrow NeutrophilMeasuresMediatingMedicationMendelian diseaseMendelian disorderMendelian genetic disorderMethodsMoAb CD20ModelingModern ManMonkeysMonoclonal AntibodiesMonoclonal Antibody CD20Myeloid CellsNauseaNeutrophilic GranulocyteNeutrophilic LeukocyteOrgan TransplantationOrgan TransplantsPathway interactionsPatientsPeptidasesPeptide HydrolasesPharmaceutical PreparationsPhase 1 Clinical TrialsPhase I Clinical TrialsPlasmapheresisPlatelet TransfusionPltsPolymorphonuclear CellPolymorphonuclear LeukocytesPolymorphonuclear NeutrophilsPopulationPre-Clinical ModelPreclinical ModelsPreclinical TestingProtease GeneProteasesProtein EngineeringProteinasesProteolytic EnzymesProteomicsPseudohypertrophic Muscular DystrophyPyrexiaRapamuneRapamycinReagentRecombinant ProteinsRecombinant adeno-associated virusRecombinant adeno-associated virus (rAAV)RecombinantsRegimenReportingRhesusRhesus MacaqueRhesus MonkeyRituxanRoleSafetySerious Adverse EventSerotypingSevere Adverse EventSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSirolimusT-Cell ActivationT-CellsT-LymphocyteTherapeutic Plasma ExchangeTherapeutic PlasmapheresisThrombocytopeniaThrombopeniaTissuesToxic effectToxic effect on liver cellsToxicitiesVeiled CellsVirusVomitingX Linked Vacuolar Cardiomyopathy and MyopathyX-linked dilated cardiomyopathyX-linked muscular dystrophyX-linked recessive muscular dystrophyactivate T cellsactivated B cellsacute kidney injuryadeno-associated viral vectoradeno-associated virus vectoranamnestic reactionanti-CD20antibody-based immunityautoimmune conditionautoimmune disorderautoimmunity diseasebenign X-linked recessive muscular dystrophybiological signal transductioncase-by-case basischildhood pseudohypertrophic muscular dystrophyclassic X-linked recessive muscular dystrophyclinical applicabilityclinical applicationclinical translationclinically translatablecomplement pathway regulationcomplementationcytokinedelivery vectordelivery vehicledetermine efficacydevelopmentaldrug/agentefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationevaluate efficacyexamine efficacyfebrilefebrisfirst in manfirst-in-humanflow cytophotometrygene repair therapygene therapygene therapy clinical trialgene transfer vectorgene-based therapygenetic protein engineeringgenetic therapygenomic therapyhepatic body systemhepatic organ systemhepatic toxicityhepatoxicityhost responsehuman modelhuman subjecthumanized micehumanized mouseimmune modulating agentsimmune modulating drugimmune modulating therapeuticsimmune modulationimmune modulatorsimmune modulatory agentsimmune modulatory drugsimmune regulationimmune serumimmune system responseimmunologic reactivity controlimmunomodulating agentsimmunomodulating drugsimmunomodulator agentimmunomodulator drugimmunomodulator medicationimmunomodulator prodrugimmunomodulator therapeuticimmunomodulatoryimmunomodulatory agentsimmunomodulatory drugsimmunomodulatory moleculesimmunomodulatory therapeuticsimmunoregulationimmunoregulatorimmunoregulatoryimmunoregulatory moleculesimmunoresponseimmunotoxicityimprovedin vitro Modelin vivoinjury to the myocardiuminsightmAbsmTOR Inhibitormanage symptommild X-linked recessive muscular dystrophymodel of humanmonoclonal Absmonogenic diseasemonogenic disordermyocardial injuryneutrophilnext generationnon-human primatenonhuman primatenovelorgan allograftorgan graftorgan xenograftpathwayphase 1 trialphase I protocolphase I trialpre-clinicalpre-clinical testingpreclinicalpreconditioningpreventpreventingprogressive muscular dystrophy of childhoodprophylacticprotein designpseudohypertrophic adult muscular dystrophypseudohypertrophic muscular paralysisrAAVrecombinant AAVrituximabsecondary immune responseserious adverse experienceserious adverse reactionseropositivesingle-gene diseasesingle-gene disordersocial rolesuccesssymptom managementthromboticthymus derived lymphocytetoxic reaction in immunologytranscriptomicsvector
Description preview
Abstract
Recombinant AAV vectors have emerged as promising gene delivery vehicles in the treatment of monogenic
disorders. With 6 different FDA approved AAV-based therapies, many additional disease targets requiring
systemic dosing continue advancing towards the clinic. However, immune responses arising from prior natural
AAV exposure or nascent…
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