2024
Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition
Rackear M, Quijano E, Ianniello Z, Colón-Ríos D, Krysztofiak A, Abdullah R, Liu Y, Rogers F, Ludwig D, Dwivedi R, Bleichert F, Glazer P. Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition. Oncotarget 2024, 15: 699-713. PMID: 39352803, PMCID: PMC11444335, DOI: 10.18632/oncotarget.28651.Peer-Reviewed Original ResearchConceptsTumor targetingMonoclonal antibody therapyTumor-specific targetingCell uptakeNucleic acid bindingCell surface antigensAntibody therapyHuman variantsClinical successCell-penetrating antibodiesAcid bindingSystemic administrationSurface antigensTumorRAD51 inhibitionAntibody platformMechanism of cell penetrationBind RAD51AntibodiesFull-lengthSpecific targetsCell penetrationDisease targetsCellsAutoantibodies
2022
The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus
Jimenez-Sainz J, Krysztofiak A, Garbarino J, Rogers F, Jensen RB. The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus. Frontiers In Genetics 2022, 13: 884210. PMID: 35711920, PMCID: PMC9197106, DOI: 10.3389/fgene.2022.884210.Peer-Reviewed Original ResearchDominant-negative alleleDNA damage responseDNA repair functionDNA strand exchangeHomology-directed repairGenome instabilityCellular functionsDamage responseDNA bindingNegative allelesStrand exchangeRepair functionGermline missense variantsCell survivalFunction mutationsMissense variantsRAD51Pathogenic allelesSimple lossPARP inhibitorsCytoplasmProteinAllelesHomologyDNA
2021
Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair
Dow J, Krysztofiak A, Liu Y, Colon-Rios DA, Rogers FA, Glazer PM. Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair. Molecular Cancer Research 2021, 19: 2057-2067. PMID: 34535560, PMCID: PMC8642278, DOI: 10.1158/1541-7786.mcr-21-0456.Peer-Reviewed Original ResearchConceptsHistone deacetylase inhibitor vorinostatPatient-derived tumor xenograftsHomology-directed repairIsocitrate dehydrogenase 1/2 mutationsHistone deacetylase inhibitionIDH1 mutant cellsGreater cell deathHDACi treatmentInhibitor vorinostatTumor xenograftsDeacetylase inhibitionIDH1/2 mutationsPotential biomarkersSpecific cancersMutant cancersCancerCancer cellsDNA repair defectsMalignancyVorinostatDNA double-strand breaksGliomasHistone hypermethylationCell deathPARPiDirect targeting of amplified gene loci for proapoptotic anticancer therapy
Kaushik Tiwari M, Colon-Rios DA, Tumu HCR, Liu Y, Quijano E, Krysztofiak A, Chan C, Song E, Braddock DT, Suh HW, Saltzman WM, Rogers FA. Direct targeting of amplified gene loci for proapoptotic anticancer therapy. Nature Biotechnology 2021, 40: 325-334. PMID: 34711990, PMCID: PMC8930417, DOI: 10.1038/s41587-021-01057-5.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksTriplex-forming oligonucleotidesDNA damage responseDouble-strand breaksDrug resistanceGene amplificationP53-independent apoptosisHER2-positive breastOvarian cancer modelHuman tumor xenograftsInduction of apoptosisGenomic lociNumber of drugsCellular functionsDamage responseGene locusProtein productsHER2-positive cancer cellsDriver genesClinical efficacyCombat drug resistanceDNA damageHER2 amplificationTherapeutic strategiesTumor xenografts
2020
A DNA Repair Inhibitor Isolated from an Ecuadorian Fungal Endophyte Exhibits Synthetic Lethality in PTEN-Deficient Glioblastoma
Adaku N, Park HB, Spakowicz DJ, Tiwari MK, Strobel SA, Crawford JM, Rogers FA. A DNA Repair Inhibitor Isolated from an Ecuadorian Fungal Endophyte Exhibits Synthetic Lethality in PTEN-Deficient Glioblastoma. Journal Of Natural Products 2020, 83: 1899-1908. PMID: 32407116, DOI: 10.1021/acs.jnatprod.0c00012.Peer-Reviewed Original ResearchConceptsPTEN-deficient glioblastoma cellsPTEN-deficient cancersTumor suppressor PTENImportant molecular toolPTEN-deficient glioblastomaInhibitor of DNAHuman cancer developmentDNA repair inhibitorsFungal endophytesBreak repairGenomic levelSuppressor PTENMolecular toolsEndophytic fungiSynthetic lethalityPTEN deficiencyGlioblastoma cellsRepair inhibitorsCancer developmentPTEN lossCurrent cancer treatmentsLarger patient populationTherapeutic leadsMedicinal plantsNew therapeutic leads
2016
Triplex structures induce DNA double strand breaks via replication fork collapse in NER deficient cells
Tiwari M, Adaku N, Peart N, Rogers FA. Triplex structures induce DNA double strand breaks via replication fork collapse in NER deficient cells. Nucleic Acids Research 2016, 44: 7742-7754. PMID: 27298253, PMCID: PMC5027492, DOI: 10.1093/nar/gkw515.Peer-Reviewed Original ResearchConceptsDouble-strand breaksReplication fork collapseFork collapseGenomic instabilityReplication-associated double-strand breaksDNA replication fork progressionNucleotide excision repair proteinsTriplex structureRobust DNA damage responseDNA double-strand breaksReplication fork progressionReplication fork stabilityStrand breaksReplication fork integrityXPC-deficient cellsDNA damage responseMirror repeat sequencesExcision repair proteinsMore DSBsNER-deficient cellsDamage recognition proteinsGenomic integrityDual phosphorylationFork stabilityFork integrityImaging 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
2014
Improved bioactivity of G-rich triplex-forming oligonucleotides containing modified guanine bases
Rogers FA, Lloyd JA, Tiwari MK. Improved bioactivity of G-rich triplex-forming oligonucleotides containing modified guanine bases. Artificial DNA PNA & XNA 2014, 5: e27792. PMID: 25483840, PMCID: PMC4014521, DOI: 10.4161/adna.27792.Peer-Reviewed Original ResearchConceptsMobility gel shift assaysDNA double-strand breaksTarget sequenceGel shift assaysDouble-strand breaksGene-targeted mutagenesisActivation of apoptosisG-quadruplex formationGenomic modificationsDNA repairShift assaysReporter geneMolecular mechanismsPolypurine sequenceStrand breaksTriplex technologyTarget siteMutagenesisTriplex structureGenesGuanine baseTriplex formationGuanine basesSequenceAG30
2013
Triplex-induced DNA damage response.
Rogers FA, Tiwari MK. Triplex-induced DNA damage response. The Yale Journal Of Biology And Medicine 2013, 86: 471-8. PMID: 24348211, PMCID: PMC3848101.Peer-Reviewed Original ResearchConceptsDNA damage responseGenomic integrityDamage responseCellular pathwaysCellular DNA damage responseDNA damageAppropriate cellular responsesPro-apoptotic factorsCell cycle arrestDNA repairDNA strand breaksCellular responsesCycle arrestDamage sitesStrand breaksPathwayApoptosisHelical structureComplex seriesCentral roleTriplex formationXPDPhosphorylationΓH2AXDNAXPD-dependent activation of apoptosis in response to triplex-induced DNA damage
Tiwari M, Rogers FA. XPD-dependent activation of apoptosis in response to triplex-induced DNA damage. Nucleic Acids Research 2013, 41: 8979-8994. PMID: 23913414, PMCID: PMC3799437, DOI: 10.1093/nar/gkt670.Peer-Reviewed Original ResearchConceptsDouble-strand breaksStrand breaksGenomic integrityPro-apoptotic pathwaysHuman genomeTyrosine 142DNA repairDNA sequencesGenomic instabilityDNA strand breaksNoncanonical structuresCancer initiationDNA damageDamage sitesΓH2AX fociHelical distortionApoptosisTriplex structureCentral rolePathwayXPDGenomeTriplexesPhosphorylationΓH2AX
2012
Local Delivery of Gene-Modifying Triplex-Forming Molecules to the Epidermis
Rogers FA, Hu RH, Milstone LM. Local Delivery of Gene-Modifying Triplex-Forming Molecules to the Epidermis. Journal Of Investigative Dermatology 2012, 133: 685-691. PMID: 23014335, PMCID: PMC3532560, DOI: 10.1038/jid.2012.351.Peer-Reviewed Original ResearchConceptsIntradermal deliveryHairless miceTransgenic miceBasal keratinocytesMethod of deliveryNuclei of keratinocytesIntraperitoneal administrationSitu gene correctionBack skinLocal deliveryMiceDisease-causing genesEpidermal keratinocytesKeratinocytesLocal administrationAdministrationDeliverySkinEpidermisDays
2011
Targeted Disruption of the CCR5 Gene in Human Hematopoietic Stem Cells Stimulated by Peptide Nucleic Acids
Schleifman EB, Bindra R, Leif J, del Campo J, Rogers FA, Uchil P, Kutsch O, Shultz LD, Kumar P, Greiner DL, Glazer PM. Targeted Disruption of the CCR5 Gene in Human Hematopoietic Stem Cells Stimulated by Peptide Nucleic Acids. Cell Chemical Biology 2011, 18: 1189-1198. PMID: 21944757, PMCID: PMC3183429, DOI: 10.1016/j.chembiol.2011.07.010.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsHIV-1CCR5 geneHIV-1-infected individualsHIV-1 infectionGene modificationHIV-1 entryCCR5-Delta32 mutationImmune system functionStem cellsCCR5 knockoutMonths posttransplantationChemokine receptorsHuman hematopoietic stem cellsTherapeutic strategiesSubsequent engraftmentGenome modificationProtein levelsHuman cellsTargeted disruptionCCR5Peptide nucleic acidInfectionNucleic acidsCellsTargeted Gene Modification of Hematopoietic Progenitor Cells in Mice Following Systemic Administration of a PNA-peptide Conjugate
Rogers FA, Lin SS, Hegan DC, Krause DS, Glazer PM. Targeted Gene Modification of Hematopoietic Progenitor Cells in Mice Following Systemic Administration of a PNA-peptide Conjugate. Molecular Therapy 2011, 20: 109-118. PMID: 21829173, PMCID: PMC3255600, DOI: 10.1038/mt.2011.163.Peer-Reviewed Original ResearchConceptsGene modificationGene therapyHematopoietic stem cell gene therapyStem cell gene therapyGenomic modificationsVivo gene therapyCell gene therapyTargeted gene modificationVivo gene modificationHematopoietic progenitor cellsPeptide nucleic acidSystemic administrationBone marrowGene-targeting strategiesProgenitor cellsPrimary recipient miceStem cell mobilizationEx vivo manipulationSickle cell anemiaLymphoid cell lineagesDonor miceRecipient miceHematologic disordersInvasive alternativeCell mobilizationXPD‐Dependent induction of apoptosis in cells with DNA containing triple helical repeats
Rogers F, Kaushik M. XPD‐Dependent induction of apoptosis in cells with DNA containing triple helical repeats. The FASEB Journal 2011, 25: 310.3-310.3. DOI: 10.1096/fasebj.25.1_supplement.310.3.Peer-Reviewed Original ResearchDNA repairH-DNAAltered helical structureNucleotide excision repair pathwayExcision repair pathwayTriple helical repeatsGenomic integrityPro-apoptotic pathwaysHuman genomeInduction of mutationsDNA sequencesRepair pathwaysHelical repeatBase pairsDNA damageIntricate balanceHelical distortionRepair synthesisTriplex structureApoptosisHelical structureCentral roleTriplex formationPathwayInduction
2009
Targeted correction of a thalassemia-associated β-globin mutation induced by pseudo-complementary peptide nucleic acids
Lonkar P, Kim KH, Kuan JY, Chin JY, Rogers FA, Knauert MP, Kole R, Nielsen PE, Glazer PM. Targeted correction of a thalassemia-associated β-globin mutation induced by pseudo-complementary peptide nucleic acids. Nucleic Acids Research 2009, 37: 3635-3644. PMID: 19364810, PMCID: PMC2699504, DOI: 10.1093/nar/gkp217.Peer-Reviewed Original ResearchConceptsBeta-globin geneNucleotide excision repair factorsAltered helical structureExcision repair factorsSingle base-pair modificationTriplex-forming peptide nucleic acidsPseudo-complementary peptide nucleic acidsDisease-related genesDonor DNA fragmentsComplementary DNA sequenceNucleic acidsProper splicingRepair factorsSite-specific bindingMammalian cellsSite-specific modificationDNA repairDNA sequencesGene targetingSecond intronDNA fragmentsHuman cellsTriple helix formationGene correctionHuman fibroblast cells
2006
1031. Improved Intranuclear Delivery of PNA- Peptide Conjugates Designed for Chromosomal Gene Targeting
Rogers F, Glazer P. 1031. Improved Intranuclear Delivery of PNA- Peptide Conjugates Designed for Chromosomal Gene Targeting. Molecular Therapy 2006, 13: s396. DOI: 10.1016/j.ymthe.2006.08.1126.Peer-Reviewed Original Research1030. Pyrazolo[3,4-d]Pyrimidine Guanine Base Substitution in Triplex Forming Oligonucleotides Improves Target Specificity and Chromosomal Mutagenesis
Chin J, Lloyd J, Rogers F, Glazer P. 1030. Pyrazolo[3,4-d]Pyrimidine Guanine Base Substitution in Triplex Forming Oligonucleotides Improves Target Specificity and Chromosomal Mutagenesis. Molecular Therapy 2006, 13: s396. DOI: 10.1016/j.ymthe.2006.08.1125.Peer-Reviewed Original Research
2005
Triplex-forming oligonucleotides as potential tools for modulation of gene expression.
Rogers FA, Lloyd JA, Glazer PM. Triplex-forming oligonucleotides as potential tools for modulation of gene expression. Anti-Cancer Agents In Medicinal Chemistry 2005, 5: 319-26. PMID: 16101484, DOI: 10.2174/1568011054222300.Peer-Reviewed Original ResearchConceptsGene expressionAltered helical structureTarget sequenceSequence-specific mannerGenome modificationGenomic modificationsRepair pathwaysDNA-reactive compoundsOligonucleotide bindsDuplex DNAMajor grooveSpecific sitesHelical structureDual roleExpressionPossible roleCancer therapySequenceTFOGenomeTriplexesPolypyrimidineNumber of studiesDNABindsDistance and Affinity Dependence of Triplex-Induced Recombination †
Knauert MP, Lloyd JA, Rogers FA, Datta HJ, Bennett ML, Weeks DL, Glazer PM. Distance and Affinity Dependence of Triplex-Induced Recombination †. Biochemistry 2005, 44: 3856-3864. PMID: 15751961, DOI: 10.1021/bi0481040.Peer-Reviewed Original Research
2004
Peptide conjugates for chromosomal gene targeting by triplex-forming oligonucleotides
Rogers FA, Manoharan M, Rabinovitch P, Ward DC, Glazer PM. Peptide conjugates for chromosomal gene targeting by triplex-forming oligonucleotides. Nucleic Acids Research 2004, 32: 6595-6604. PMID: 15602001, PMCID: PMC545466, DOI: 10.1093/nar/gkh998.Peer-Reviewed Original ResearchConceptsMutation frequencyGene-targeted mutagenesisHomeodomain of AntennapediaDNA-binding moleculesChromosomal genesThird helixTarget genesChromosomal DNABiological activityAntpCell-penetrating peptidesGene expressionControl genesTransport peptideCellular uptakeAntigene compoundsGenesConfocal microscopyIntranuclear deliveryTFODose-responsive mannerHomeodomainAntennapediaOligonucleotideMutagenesis
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