2012
Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis
Zhang P, Huang A, Morales-Ruiz M, Starcher BC, Huang Y, Sessa WC, Niklason LE, Giordano FJ. Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis. Human Gene Therapy 2012, 23: 1186-1199. PMID: 22891920, PMCID: PMC3498887, DOI: 10.1089/hum.2011.201.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAortic Stenosis, SupravalvularCell LineCell MovementCell ProliferationDosage Compensation, GeneticElastinGene ExpressionGene Expression RegulationHaploinsufficiencyHumansMutationNonsense Mediated mRNA DecayOrgan SpecificityProtein EngineeringTranscriptional ActivationWilliams SyndromeZinc FingersConceptsZinc finger protein transcription factorsTranscriptional activationWild-type alleleWilliams-Beuren syndromeMutant allelesEngineered Zinc Finger ProteinsElastin geneTargeted transcriptional activationCompensatory expressionSplice variantsZinc finger proteinProtein transcription factorsNonsense-mediated decayWild-type cellsMultiple splice variantsElastin expressionGene replacement strategyMutant proteinsHaploinsufficient genesTranscription factorsComplex genesNatural stoichiometryDistinct genetic syndromesGenesGenetic diseasesA Designed Zinc-finger Transcriptional Repressor of Phospholamban Improves Function of the Failing Heart
Zhang HS, Liu D, Huang Y, Schmidt S, Hickey R, Guschin D, Su H, Jovin IS, Kunis M, Hinkley S, Liang Y, Hinh L, Spratt SK, Case CC, Rebar EJ, Ehrlich BE, Ehrlich B, Gregory P, Giordano F. A Designed Zinc-finger Transcriptional Repressor of Phospholamban Improves Function of the Failing Heart. Molecular Therapy 2012, 20: 1508-1515. PMID: 22828502, PMCID: PMC3412484, DOI: 10.1038/mt.2012.80.Peer-Reviewed Original ResearchConceptsHeart failureZinc finger protein transcription factorsSingle gene regulationZinc finger transcriptional repressorDiverse DNA sequencesProtein transcription factorsDisease-related genesDisease-related proteinsGene repressionZFP TFsTranscriptional repressorTranscription factorsDNA sequencesPotent repressionPLN expressionHuman diseasesRepressorContractile functionDrug targetsFailing HeartTherapeutic inhibitionAnimal modelsReuptake kineticsRepressionTherapeutic interventions
2002
Induction of angiogenesis in a mouse model using engineered transcription factors
Rebar EJ, Huang Y, Hickey R, Nath AK, Meoli D, Nath S, Chen B, Xu L, Liang Y, Jamieson AC, Zhang L, Spratt SK, Case CC, Wolffe A, Giordano FJ. Induction of angiogenesis in a mouse model using engineered transcription factors. Nature Medicine 2002, 8: 1427-1432. PMID: 12415262, DOI: 10.1038/nm1202-795.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAngiogenesis Inducing AgentsAnimalsDrug DesignGene Expression RegulationGenetic TherapyMiceModels, AnimalMolecular Sequence DataNeovascularization, PhysiologicProtein EngineeringRecombinant ProteinsTranscription FactorsVascular Endothelial Growth Factor AZinc FingersConceptsTranscription factorsEndogenous genesZinc finger protein transcription factorsProtein transcription factorsWhole-organism modelDNA sequencesInduced expressionGenesInduction of angiogenesisZFPExpression of VEGFAProtein VEGFExpressionGrowth factorStimulation of angiogenesisTissue cultureVascular endothelial growth factorExperimental wound healingEndothelial growth factorWound healingNatural arraysAngiogenesisVivoCDNAMouse model