Employing a Gain-of-Function Factor IX Variant R338L to Advance the Efficacy and Safety of Hemophilia B Human Gene Therapy: Preclinical Evaluation Supporting an Ongoing Adeno-Associated Virus Clinical Trial
Monahan PE, Sun J, Gui T, Hu G, Hannah WB, Wichlan DG, Wu Z, Grieger JC, Li C, Suwanmanee T, Stafford DW, Booth CJ, Samulski JJ, Kafri T, McPhee SW, Samulski RJ. Employing a Gain-of-Function Factor IX Variant R338L to Advance the Efficacy and Safety of Hemophilia B Human Gene Therapy: Preclinical Evaluation Supporting an Ongoing Adeno-Associated Virus Clinical Trial. Human Gene Therapy 2015, 26: 69-81. PMID: 25419787, PMCID: PMC4326268, DOI: 10.1089/hum.2014.106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingCapsidClinical Trials as TopicDependovirusDisease Models, AnimalDrug Evaluation, PreclinicalFactor IXGene ExpressionGenetic EngineeringGenetic TherapyGenetic VectorsHemophilia BHemorrhageHumansLiverMaleMiceMice, Inbred C57BLMice, KnockoutRecombinant ProteinsTailTissue DistributionVirionConceptsHuman clinical trialsClinical trialsVector deliveryDose-dependent inflammationAbility of adenoLiver infiltratesMacrovascular thrombosisHemophilic arthropathyClinical morbidityHistopathological findingsMice 8Mild hemophilia BHemophilic miceEfficacy profileNormal micePreclinical studiesIdentical dosesMarked tropismPreclinical evaluationClinical successFIX antibodyTail transectionFIX activityBiodistribution evaluationFunction variants