2024
Engineered Branaplam Aptamers Exploit Structural Elements from Natural Riboswitches
Mohsen M, Midy M, Balaji A, Breaker R. Engineered Branaplam Aptamers Exploit Structural Elements from Natural Riboswitches. ACS Chemical Biology 2024, 19: 1447-1452. PMID: 38954594, PMCID: PMC11267568, DOI: 10.1021/acschembio.4c00358.Peer-Reviewed Original ResearchRNA poolRiboswitch aptamerAptamer candidatesPaired elementsIn vitro selectionNatural riboswitchesHuntington's diseaseThiamine pyrophosphateAptamer developmentRiboswitchDrug candidatesAptamerStructural scaffoldBranaplamRNASpinal muscular atrophyImproved bindingTreat spinal muscular atrophySmall moleculesBioavailability characteristicsDissociation constantPseudoknotMuscular atrophyStructural elementsPool
2023
8-oxoguanine riboswitches in bacteria detect and respond to oxidative DNA damage
Dhakal S, Kavita K, Panchapakesan S, Roth A, Breaker R. 8-oxoguanine riboswitches in bacteria detect and respond to oxidative DNA damage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2307854120. PMID: 37748066, PMCID: PMC10556655, DOI: 10.1073/pnas.2307854120.Peer-Reviewed Original ResearchConceptsAptamer domainGene expressionLigand specificityOxidative damageLigand-binding pocketRiboswitch classesFamilies of bacteriaRare variantsRiboswitch aptamerCertain oxidative stressesExposure of cellsOxidative DNA damageRiboswitchGene associationsRNA aptamersDNA damageNucleotide poolBacteriaTarget ligandsOxidative stressMutationsNumerous alterationsPurine derivativesExpressionVariantsIn vitro Selection and in vivo Testing of Riboswitch-inspired Aptamers
Mohsen M, Breaker R. In vitro Selection and in vivo Testing of Riboswitch-inspired Aptamers. Bio-protocol 2023, 13: e4775. PMID: 37456339, PMCID: PMC10338711, DOI: 10.21769/bioprotoc.4775.Peer-Reviewed Original ResearchAptamer candidatesSubsequent biochemical validationComplex cellular environmentVitro selection protocolSelfish sequencesRiboswitch aptamerNext-generation sequencingRNA poolBacterial cell cultureExpression platformCellular environmentBacterial cellsBiochemical validationStructural scaffoldLigand candidatesCell culturesSelection protocolAptamerRiboswitchNew ligandsSelectionBioinformaticsSequencingScaffold typesSequenceExploiting natural riboswitches for aptamer engineering and validation
Mohsen M, Midy M, Balaji A, Breaker R. Exploiting natural riboswitches for aptamer engineering and validation. Nucleic Acids Research 2023, 51: 966-981. PMID: 36617976, PMCID: PMC9881172, DOI: 10.1093/nar/gkac1218.Peer-Reviewed Original ResearchConceptsNatural riboswitchesRiboswitch aptamerReporter gene expressionSecondary structure featuresRNA poolExpression platformVivo functionGene expressionSurvival mechanismRNA sequencesStructural featuresRiboswitchAptamer selectionSmall moleculesSequenceAptamerCellsGuanineTest tubeFuture effortsSelectionSelection strategyExpressionPoolAptamer engineering
2019
Genome‐wide Discovery of Rare Riboswitches in Bacteria
Arachchilage G, Atilho R, Stav S, Higgs G, Breaker R. Genome‐wide Discovery of Rare Riboswitches in Bacteria. The FASEB Journal 2019, 33: 778.8-778.8. DOI: 10.1096/fasebj.2019.33.1_supplement.778.8.Peer-Reviewed Original ResearchRiboswitch candidatesBacterial genomesGC-rich intergenic regionsDifferent bacterial genomesGenome-wide discoverySequenced bacterial genomesNascent RNA transcriptsRiboswitch classesThiamin biosynthesisRiboswitch aptamerStructured ncRNAsNcRNA classesIntergenic regionHydroxymethylpyrimidine pyrophosphateRiboswitchBioinformatics pipelineRNA transcriptsTranscription processComputational pipelinePhysiological pathwaysConformational changesNcRNAsGenomeFASEB JournalHoward Hughes Medical Institute