2016
Imaging Functional Nucleic Acid Delivery to Skin
Kaspar RL, Hickerson RP, González-González E, Flores MA, Speaker TP, Rogers FA, Milstone LM, Contag CH. Imaging Functional Nucleic Acid Delivery to Skin. Methods In Molecular Biology 2016, 1372: 1-24. PMID: 26530911, DOI: 10.1007/978-1-4939-3148-4_1.Peer-Reviewed Original ResearchConceptsNucleic acid deliveryNucleic acid-based therapiesAcid deliveryAcid-based therapiesFunctional deliveryFunctional nucleic acid deliveryTherapeutic nucleic acidsNucleic acidsOptical imaging technologiesReal-time monitoringTriplex nucleic acidsInteraction of lightMonogenic skin diseasesLight-tissue interactionsGene editingGene silencingOptical imagingNoninvasive imaging technologyTopical deliveryTime monitoringImaging technologyReporter geneLayered structureGeneral strategyEnzymatic reactions
2012
Inhibition of CD44 Gene Expression in Human Skin Models, Using Self-Delivery Short Interfering RNA Administered by Dissolvable Microneedle Arrays
Lara MF, González-González E, Speaker TJ, Hickerson RP, Leake D, Milstone LM, Contag CH, Kaspar RL. Inhibition of CD44 Gene Expression in Human Skin Models, Using Self-Delivery Short Interfering RNA Administered by Dissolvable Microneedle Arrays. Human Gene Therapy 2012, 23: 816-823. PMID: 22480249, PMCID: PMC3413896, DOI: 10.1089/hum.2011.211.Peer-Reviewed Original ResearchConceptsTransgenic mouse modelInhibition of CD44CD44-specific antibodiesCD44 mRNA levelsDissolvable microneedle arraysGene expressionMouse modelXenograft modelSkin disordersCD44 gene expressionHuman skin modelTarget cellsMRNA levelsHuman skin equivalentsKeratinocyte membraneTreatmentInhibitionStratum corneumTarget gene expressionSiRNASkin equivalentsEpidermal equivalentsMicroneedle arraysSkin modelExpression
2010
Development of Quantitative Molecular Clinical End Points for siRNA Clinical Trials
Hickerson RP, Leachman SA, Pho LN, Gonzalez-Gonzalez E, Smith FJ, McLean WH, Contag CH, Leake D, Milstone LM, Kaspar RL. Development of Quantitative Molecular Clinical End Points for siRNA Clinical Trials. Journal Of Investigative Dermatology 2010, 131: 1029-1036. PMID: 21191405, DOI: 10.1038/jid.2010.372.Peer-Reviewed Original ResearchConceptsClinical trialsPachyonychia congenitaEnd pointPhase 1b clinical trialClinical end pointsRare skin disorderMolecular end pointsTypes of trialsImmune surveillancePatient-derived keratinocytesSkin disordersSustained inhibitionTreatment resultsRNAi-based therapeuticsRNA interferenceMRNA levelsTrialsTotal RNAHuman skinKeratinocyte culturesMRNAAmplifiable mRNATherapeuticsInhibitorsInhibition
2009
First-in-human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder
Leachman SA, Hickerson RP, Schwartz ME, Bullough EE, Hutcherson SL, Boucher KM, Hansen CD, Eliason MJ, Srivatsa GS, Kornbrust DJ, Smith FJ, McLean WI, Milstone LM, Kaspar RL. First-in-human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder. Molecular Therapy 2009, 18: 442-446. PMID: 19935778, PMCID: PMC2839285, DOI: 10.1038/mt.2009.273.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaPhase Ib clinical trialSubjective patient assessmentPhase Ib trialDose-escalation trialClinical efficacy measuresAutosomal dominant syndromeIb trialAdverse eventsWashout periodPatient assessmentEfficacy measuresPlantar callusClinical trialsPlantar keratodermaOpposite footSkin disordersSkin diseasesClinical settingDominant syndromeSatisfactory treatmentAdditional studiesTrialsGenetic disordersSiRNA
2008
Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita
Leachman SA, Hickerson RP, Hull PR, Smith FJ, Milstone LM, Lane EB, Bale SJ, Roop DR, McLean WH, Kaspar RL. Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita. Journal Of Dermatological Science 2008, 51: 151-157. PMID: 18495438, PMCID: PMC2587483, DOI: 10.1016/j.jdermsci.2008.04.003.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaQuantitative RT-PCRRT-PCRReal-time RT-PCRQuantitative real-time RT-PCRClinical efficacyGenetic skin disordersClinical trialsCandidate siRNASkin disordersRNA interferenceNovel therapeuticsPotent inhibitionTherapeutic siRNAsClinical applicationDisordersGenetic disordersPhysiciansCongenitaMutant allelesSiRNAHuman diseasesKeratin disordersPatientsDisease
2007
Single-Nucleotide-Specific siRNA Targeting in a Dominant-Negative Skin Model
Hickerson RP, Smith FJ, Reeves RE, Contag CH, Leake D, Leachman SA, Milstone LM, McLean WH, Kaspar RL. Single-Nucleotide-Specific siRNA Targeting in a Dominant-Negative Skin Model. Journal Of Investigative Dermatology 2007, 128: 594-605. PMID: 17914454, DOI: 10.1038/sj.jid.5701060.Peer-Reviewed Original ResearchConceptsWild-type gene expressionBicistronic reporter constructFilament formationDominant-negative genetic disordersNumerous genetic disordersGenetic disordersKeratin filament formationRNA interferenceMutant formsReporter constructsGene expressionMutant mRNAFluorescent reportersMutant allelesCell culture modelSiRNAsSimultaneous expressionK6aK mutationPachyonychia congenitaExpressionCulture modelHuman keratinocytesSiRNASelective inhibition
2005
Gene Therapy for Autosomal Dominant Disorders of Keratin
Lewin AS, Glazer PM, Milstone LM. Gene Therapy for Autosomal Dominant Disorders of Keratin. Journal Of Investigative Dermatology Symposium Proceedings 2005, 10: 47-61. PMID: 16250209, DOI: 10.1111/j.1087-0024.2005.10207.x.Commentaries, Editorials and LettersMeSH KeywordsAnimalsDarier DiseaseDependovirusEctodermal DysplasiaEpidermolysis Bullosa SimplexGene SilencingGene TargetingGenes, DominantGenetic TherapyGenetic VectorsHumansKeratinsKeratoderma, PalmoplantarMiceMutationNails, MalformedOligonucleotides, AntisenseRNA InterferenceRNA, CatalyticRNA, Small InterferingConceptsRNA knockdown approachGene correctionGene therapyViral vectorsEpidermal skin cellsKeratin diseasesKnockdown approachRNA interferenceGene expressionEpidermolysis bullosa simplexToxic proteinsDominant mutationsGenetic diseasesGenetic therapiesKeratin filamentsEpidermal diseasesGenetic defectsTissue cultureSelective inhibitorSkin cellsAttractive alternativeAutosomal dominant disorderRecent innovationsDominant disorderNear future