2024
Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation
Gupta A, Barone C, Quijano E, Piotrowski-Daspit A, Perera J, Riccardi A, Jamali H, Turchick A, Zao W, Saltzman W, Glazer P, Egan M. Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation. Journal Of Cystic Fibrosis 2024 PMID: 39107154, DOI: 10.1016/j.jcf.2024.07.009.Peer-Reviewed Original ResearchCystic fibrosis transmembrane conductance regulatorCystic fibrosis transmembrane conductance regulator geneF508del-CFTR mutationPeptide nucleic acidCFBE cellsBronchial epithelial cellsCystic fibrosisTriplex-forming peptide nucleic acidsDonor DNACFTR mutationsEpithelial cellsCFTR functionMutations associated with genetic diseasesPrimary nasal epithelial cellsAnalysis of genomic DNAGenetic diseasesIncreased CFTR functionDevelopment of peptide nucleic acidsImprove CFTR functionTransmembrane conductance regulatorAutosomal recessive genetic diseaseNasal epithelial cellsAir-liquid interfaceCystic fibrosis bronchial epithelial cellsHuman bronchial epithelial cellsPeptide Nucleic Acid-Mediated Regulation of CRISPR-Cas9 Specificity
Carufe K, Economos N, Glazer P. Peptide Nucleic Acid-Mediated Regulation of CRISPR-Cas9 Specificity. Nucleic Acid Therapeutics 2024, 34: 245-256. PMID: 39037032, DOI: 10.1089/nat.2024.0007.Peer-Reviewed Original ResearchPeptide nucleic acidProtospacer adjacent motifAllele-specific mannerDegree of homologyWild-type sequencePAM-proximal regionSynthetic peptide nucleic acidOff-target sitesSpacer sequencesAdjacent motifMutant allelesCas9 cuttingBase pairsCas9 activityCRISPR technologyAutosomal dominant diseaseGRNACRISPR applicationsNucleic acidsBinding positionDominant diseaseSequenceDeliberate mismatchGene therapy
2022
Nanoparticle‐mediated genome editing in single‐cell embryos via peptide nucleic acids
Putman R, Ricciardi A, Carufe K, Quijano E, Bahal R, Glazer P, Saltzman W. Nanoparticle‐mediated genome editing in single‐cell embryos via peptide nucleic acids. Bioengineering & Translational Medicine 2022, 8: e10458. PMID: 37206203, PMCID: PMC10189434, DOI: 10.1002/btm2.10458.Peer-Reviewed Original ResearchSingle-cell embryosPeptide nucleic acidGene editingNucleic acidsNanoparticlesGross developmental abnormalitiesGenome editingNormal physiological developmentOff-target effectsDonor DNAGenetic diseasesConcept workEmbryosGenomic effectsDevelopmental abnormalitiesNormal growthEmbryogenesisPhysiological developmentEditingUnderlying mutationPreimplantation genetic diagnosisDisease pathogenesisGenetic diagnosisNormal morphologyAcid
2018
Debugging the genetic code: non-viral in vivo delivery of therapeutic genome editing technologies
Piotrowski-Daspit AS, Glazer P, Saltzman WM. Debugging the genetic code: non-viral in vivo delivery of therapeutic genome editing technologies. Current Opinion In Biomedical Engineering 2018, 7: 24-32. PMID: 30984891, PMCID: PMC6456264, DOI: 10.1016/j.cobme.2018.08.002.Peer-Reviewed Original ResearchGenome editingNon-viral delivery methodsCRISPR/Cas9 systemGenome engineering technologiesGenome editing technologyTherapeutic genome editingPeptide nucleic acidSpecific cell typesGenetic codeVivo deliveryCas9 systemEditing technologyEfficient deliveryGenomic mutationsCell typesPolymeric vehiclesFuture outlookDisease phenotypePrecise technologyEngineering technologyDelivery methodsNucleic acidsCell culturesEditingHereditary diseaseIn utero nanoparticle delivery for site-specific genome editing
Ricciardi AS, Bahal R, Farrelly JS, Quijano E, Bianchi AH, Luks VL, Putman R, López-Giráldez F, Coşkun S, Song E, Liu Y, Hsieh WC, Ly DH, Stitelman DH, Glazer PM, Saltzman WM. In utero nanoparticle delivery for site-specific genome editing. Nature Communications 2018, 9: 2481. PMID: 29946143, PMCID: PMC6018676, DOI: 10.1038/s41467-018-04894-2.Peer-Reviewed Original ResearchConceptsSite-specific genome editingReversal of splenomegalyPeptide nucleic acidIntra-amniotic administrationBlood hemoglobin levelsMonogenic disordersNanoparticle deliveryPolymeric nanoparticlesPostnatal elevationGestational ageHemoglobin levelsImproved survivalPediatric morbidityDisease improvementHuman β-thalassemiaReticulocyte countNormal organ developmentMouse modelNormal rangeEarly interventionGenome editingOff-target mutationsPostnatal growthGene editingVersatile method
2016
In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery
Bahal R, Ali McNeer N, Quijano E, Liu Y, Sulkowski P, Turchick A, Lu YC, Bhunia DC, Manna A, Greiner DL, Brehm MA, Cheng CJ, López-Giráldez F, Ricciardi A, Beloor J, Krause DS, Kumar P, Gallagher PG, Braddock DT, Mark Saltzman W, Ly DH, Glazer PM. In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery. Nature Communications 2016, 7: 13304. PMID: 27782131, PMCID: PMC5095181, DOI: 10.1038/ncomms13304.Peer-Reviewed Original ResearchConceptsNanoparticle deliveryGene correctionReversal of splenomegalyPeptide nucleic acidLow off-target effectsVivo correctionGenome editingOff-target effectsGene editingHaematopoietic stem cellsNucleic acidsDonor DNAStem cellsΓPNAΒ-thalassaemiaNanoparticlesDeliveryEditingSCF treatmentTriplex formation
2015
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium
McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME. Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nature Communications 2015, 6: 6952. PMID: 25914116, PMCID: PMC4480796, DOI: 10.1038/ncomms7952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsGenetic TherapyHigh-Throughput Nucleotide SequencingHumansLactic AcidMice, Inbred C57BLNanoparticlesPeptide Nucleic AcidsPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPolymersRespiratory MucosaConceptsFacile genome engineeringVivo gene deliveryBiodegradable polymer nanoparticlesTransient gene expressionNanoparticle systemsGene deliveryPolymer nanoparticlesGene correctionGenome engineeringNanoparticlesOff-target effectsPeptide nucleic acidLethal genetic disorderNucleic acidsDonor DNATarget effectsIntranasal deliveryDeliveryCystic fibrosisEngineeringOligonucleotideChloride effluxHuman cellsAirway epitheliumLung tissue
2006
Peptide Nucleic Acids as Agents to Modify Target Gene Expression and Function
Wang G, Glazer P. Peptide Nucleic Acids as Agents to Modify Target Gene Expression and Function. Medical Intelligence Unit 2006, 223-235. DOI: 10.1007/0-387-32956-0_14.Peer-Reviewed Original ResearchTarget gene expressionGene expressionMolecular mechanismsHuman diseasesGene expression regulationExpression regulationTranscription initiationDNA repairImportant genesMolecular basisTranscriptionGenesNucleic acidsExpressionAbility of PNAMutagenesisAttractive strategyPowerful methodBetter understandingRegulationMechanismPeptide nucleic acidBroad range
2003
Peptide nucleic acids as agents to modify target gene expression and function
Wang G, Glazer P. Peptide nucleic acids as agents to modify target gene expression and function. International Journal Of Peptide Research And Therapeutics 2003, 10: 335-345. DOI: 10.1007/s10989-004-4903-0.Peer-Reviewed Original Research