2025
Natural history of preexisting AAV5 antibodies in adults with hemophilia B during the lead-in of the etranacogene dezaparvovec phase 3 study
Klamroth R, Recht M, Key N, Miesbach W, Pipe S, Kaczmarek R, Drelich D, Salazar B, Le Quellec S, Monahan P, Galante N, van der Valk P, Tarrant J. Natural history of preexisting AAV5 antibodies in adults with hemophilia B during the lead-in of the etranacogene dezaparvovec phase 3 study. Molecular Therapy — Methods & Clinical Development 2025, 33: 101568. PMID: 40969675, PMCID: PMC12441693, DOI: 10.1016/j.omtm.2025.101568.Peer-Reviewed Original ResearchAAV serotype 5Adeno-associated virusLead-in periodNatural historyGene therapyAAV-based gene therapyLaboratory assessmentAnti-AAV5 antibodiesCorrelation of titersPhase 3 studyAssociated with older agePhase 3 trialNAb titersDetectable NAbsMedian titerHemophilia BNeutralizing antibodiesHemophilia B.Serotype 5HemophiliaImmunoglobulin MNAbsBinding antibodiesLead-InImmunoglobulin GDelandistrogene Moxeparvovec Gene Therapy in Individuals With Duchenne Muscular Dystrophy: Evidence in Focus: Report of the AAN Guidelines Subcommittee.
Oskoui M, Caller T, Parsons J, Servais L, Butterfield R, Bharadwaj J, Rose S, Tolchin B, Puskala Hamel K, Silsbee H, Dowling J. Delandistrogene Moxeparvovec Gene Therapy in Individuals With Duchenne Muscular Dystrophy: Evidence in Focus: Report of the AAN Guidelines Subcommittee. Neurology 2025, 105: e214014. PMID: 40737572, DOI: 10.1212/wnl.0000000000214014.Peer-Reviewed Original ResearchPilot Clinical Study Showing Abnormal Copper Metabolism in Healthy Wilson Disease Heterozygote Subjects
Benichou B, Combal J, Dogterom P, Sandahl T, D'Antiga L, Schilsky M. Pilot Clinical Study Showing Abnormal Copper Metabolism in Healthy Wilson Disease Heterozygote Subjects. Clinical And Translational Science 2025, 18: e70294. PMCID: PMC12271968, DOI: 10.1111/cts.70294.Peer-Reviewed Original ResearchHealthy volunteersGene therapyOpen-label pilot clinical studyPotential dimerizationGene repair therapyCu-transporting P-type ATPaseLife-threatening disorderDominant negative effectP-type ATPasesPilot clinical studyAutosomal recessive mannerAbnormal copper metabolismBiliary copper excretionMutant proteinsIntravenous doseCu-dependent enzymesATP7B mutationsClinical studiesATP7B functionCopper excretionRecessive mannerHeterozygote subjectsTherapyBiosynthetic incorporationTransport proteinsCompletion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years
von Drygalski A, Gomez E, Giermasz A, Castaman G, Key N, Lattimore S, Leebeek F, Miesbach W, Recht M, Monahan P, Le Quellec S, Pipe S. Completion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years. Blood Advances 2025, 9: 3543-3552. PMID: 40188458, PMCID: PMC12275190, DOI: 10.1182/bloodadvances.2024015291.Peer-Reviewed Original ResearchAdeno-associated virus serotype 5Etranacogene dezaparvovecHemophilia BRecombinant adeno-associated virus serotype 5FIX inhibitor developmentLiver-specific promoterPost-administrationSelf-administered infusionsSevere hemophilia BMulti-center trialYears post-administrationBleeding episodesOpen-labelSingle-doseSecondary endpointsIntravenous doseSingle-armGene therapyThrombotic complicationsYears post-treatmentSafety profileClinically significant elevationsAdverse eventsBleeding frequencyNeutralizing antibodiesPlain language summary of 4-year results of the GENEr8-1 clinical trial of valoctocogene roxaparvovec gene therapy for hemophilia A
Madan B, Ozelo M, Kenet G, Chou S, Dashiell-Aje E, Robinson T, Mahlangu J, Recht M, Careta F, Ruiz A, Fletcher S, Goshen D. Plain language summary of 4-year results of the GENEr8-1 clinical trial of valoctocogene roxaparvovec gene therapy for hemophilia A. Future Rare Diseases 2025, 5: 2522071. DOI: 10.1080/23995270.2025.2522071.Peer-Reviewed Original ResearchDelandistrogene Moxeparvovec Gene Therapy in Individuals With Duchenne Muscular Dystrophy: Evidence in Focus
Oskoui M, Caller T, Parsons J, Servais L, Butterfield R, Bharadwaj J, Rose S, Tolchin B, Puskala Hamel K, Silsbee H, Dowling J. Delandistrogene Moxeparvovec Gene Therapy in Individuals With Duchenne Muscular Dystrophy: Evidence in Focus. Neurology 2025, 104: e213604. PMID: 40367405, DOI: 10.1212/wnl.0000000000213604.Peer-Reviewed Original ResearchConceptsDuchenne muscular dystrophyFood and Drug AdministrationClinical trialsImmune-related side effectsMuscular dystrophyFood and Drug Administration approvalFunctional motor outcomePhase 3 clinical trialsTreatment groupsNorth Star Ambulatory Assessment scoresUS Food and Drug AdministrationMotor outcomeClinical trial dataRisk of biasClass I studiesGene therapyTreated patientsAmerican Academy of NeurologyLiver toxicityPrimary outcomeLiver injurySide effectsDrug AdministrationSafety outcomesDose exposurePrecision medicine in the pediatric and neonatal intensive care units through genomics
Duy P, Dylik B, Deniz E. Precision medicine in the pediatric and neonatal intensive care units through genomics. Current Opinion In Pediatrics 2025, 37: 211-215. PMID: 40298123, PMCID: PMC12055474, DOI: 10.1097/mop.0000000000001471.Peer-Reviewed Original ResearchConceptsNeonatal intensive care unitGenome-wide sequencing technologiesSingle nucleotide resolutionWhole-genome sequencingIntensive care unitGene therapyPrecision medicineNucleotide resolutionSequencing technologiesGenetic perturbationsGenomic medicineGenomic technologiesCare unitFDA-approved gene therapyGenetic associationGenetic diagnosisHuman disordersCritically Ill ChildrenOmics technologiesMolecular diagnosisGenetic conditionsDisease biologyClinically actionable findingsPathological workupDiagnostic adjunctScientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence
Olaghere J, Williams D, Farrar J, Büning H, Calhoun C, Ho T, Inamdar M, Liu D, Makani J, Nyarko K, Ruiz S, Tisdale J, McCune J, Boadi E, for the FDA R. Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence. Biomedicines 2025, 13: 758. PMID: 40149734, PMCID: PMC11940732, DOI: 10.3390/biomedicines13030758.Peer-Reviewed Original ResearchFood and Drug AdministrationGene therapySickle cell diseaseFDA-approved therapiesCost of therapyRegulatory convergenceGates FoundationCell diseaseTherapyDrug AdministrationMiddle-income countriesGlobal health advocatesModel disorderRegulatory gapsInternational regulatory bodiesReagan-Udall FoundationRegulated industriesGenesRegulatory bodiesCorticosteroid use to mitigate transaminitis-associated decline in FVIII levels following valoctocogene roxaparvovec gene therapy: clinical practice guidance
Konkle B, Peyvandi F, Foster G, Hermans C, La Mura V, Leavitt A, Lillicrap D, Mahlangu J, Ozelo M, Pipe S, Recht M, Srivastava A, Young G, Miesbach W. Corticosteroid use to mitigate transaminitis-associated decline in FVIII levels following valoctocogene roxaparvovec gene therapy: clinical practice guidance. Journal Of Thrombosis And Haemostasis 2025, 23: 2086-2094. PMID: 40090623, DOI: 10.1016/j.jtha.2025.02.042.Peer-Reviewed Original ResearchSevere hemophilia AValoctocogene roxaparvovecFactor VIIIGene therapyHemophilia AMarkers of hepatocyte injuryFactor VIII activity levelsCourse of corticosteroidsFactor VIII levelsElevated alanine transaminaseReduced FVIII levelsClinical practice guidanceFVIII levelsCorticosteroid useAdverse eventsClinical dataClinical trialsCorticosteroidsHepatocyte injuryAlanine transaminaseTherapyPatientsActivity levelsExpert opinionAdultsInvestigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis
Spagnolo P, Tonelli R, Mura M, Reisman W, Sotiropoulou V, Tzouvelekis A. Investigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis. Expert Opinion On Investigational Drugs 2025, 34: 61-80. PMID: 39916340, DOI: 10.1080/13543784.2025.2462592.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisGene therapyPulmonary fibrosisAssociated with tolerability issuesProgressive fibrosing interstitial lung diseaseEfficacy of gene therapyApplication of gene therapyTreatment of idiopathic pulmonary fibrosisLong-term clinical dataFibrosing interstitial lung diseaseFirst-line therapyImproved vector designInterstitial lung diseaseMitigate off-target effectsTolerated treatmentDismal prognosisClinical dataLung diseaseClinical studiesAssociated with poor qualityProfibrotic pathwaysTarget cellsTherapyFibrosisOff-target effectsCell and Gene Therapies — Improving Access and Outcomes for Medicare and Medicaid Beneficiaries
Ross J. Cell and Gene Therapies — Improving Access and Outcomes for Medicare and Medicaid Beneficiaries. New England Journal Of Medicine 2025, 392: 521-523. PMID: 39899894, DOI: 10.1056/nejmp2412955.Peer-Reviewed Original Research
2024
Ocular Gene Therapy: An Overview of Viral Vectors, Immune Responses, and Future Directions
Banou L, Sarrafpour S, Teng C, Liu J. Ocular Gene Therapy: An Overview of Viral Vectors, Immune Responses, and Future Directions. The Yale Journal Of Biology And Medicine 2024, 97: 491-503. PMID: 39703610, PMCID: PMC11650918, DOI: 10.59249/hwid7537.Peer-Reviewed Original ResearchConceptsAdeno-associated virusOcular gene therapyGene therapyFood and Drug AdministrationViral vectorsImmune responsePotential application of gene therapyClinical trialsApproval of voretigene neparvovecViral vector-based therapyApplication of gene therapyImproved delivery techniquesVector-based therapyImmune-privileged statusInduce Immune ResponsesReduced immune responseVoretigene neparvovecContralateral eyeRetinal dystrophyImmune privilegeOcular diseasesDeliver genesEye diseaseTherapeutic efficacyTherapyArtificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy
Witten J, Raji I, Manan R, Beyer E, Bartlett S, Tang Y, Ebadi M, Lei J, Nguyen D, Oladimeji F, Jiang A, MacDonald E, Hu Y, Mughal H, Self A, Collins E, Yan Z, Engelhardt J, Langer R, Anderson D. Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy. Nature Biotechnology 2024, 1-10. PMID: 39658727, PMCID: PMC12149338, DOI: 10.1038/s41587-024-02490-y.Peer-Reviewed Original ResearchLipid nanoparticlesMRNA deliveryIonizable lipidsImprove nanoparticle deliveryPulmonary gene therapyDelivery in vitroNucleic acid deliveryNeural networkGene therapyNasal mucosaNanoparticle deliveryMouse lungFerret lungsAcid deliveryMouse muscleMessage-passing neural networkDelivery technologiesIn vivoLipid designLungMiceDeliveryDeep learningMRNALipidSickle cell disease in India: the journey and hope for the future.
Gupta K, Krishnamurti L, Jain D. Sickle cell disease in India: the journey and hope for the future. Hematology 2024, 2024: 1-9. PMID: 39644008, PMCID: PMC11665512, DOI: 10.1182/hematology.2024000678.Peer-Reviewed Original ResearchConceptsSickle cell diseaseHematopoietic stem cell transplantationCell diseaseSeverity of sickle cell diseaseStem cell transplantationAcute chest syndromeVaso-occlusive crisisSurvive into adulthoodChest syndromePenicillin prophylaxisCell transplantationRenal involvementHydroxyurea therapyGene therapyClinical featuresNovel therapiesA-thalassemiaFetal HbNewborn screeningAvascular necrosisTranscranial DopplerComprehensive care programTherapyYounger ageFatal diseaseWilson Disease: Novel Diagnostic and Therapeutic Approaches
Mariño Z, Schilsky M. Wilson Disease: Novel Diagnostic and Therapeutic Approaches. Seminars In Liver Disease 2024, 45: 221-235. PMID: 39496313, DOI: 10.1055/a-2460-8999.Peer-Reviewed Original ResearchWilson's diseaseTrials of gene therapyLiver biopsy specimensDried Blood SpotsCase of WDBiliary copper excretionBiopsy specimensGene therapyDiagnostic advancesMonitoring therapyWD diagnosisNewborn screeningLiver diseaseCopper excretionTherapeutic approachesBlood spotsTherapyTherapeutic objectivesDiseaseDiagnosisLiverCopper assayPatientsExcretionDeciding between Multiple Curative Options in Sickle Cell Disease: Cost-Effectiveness of Non-Myeloablative/Reduced Intensity Conditioning Haploidentical Allo-HSCT Vs Gene Therapy Vs Standard of Care in Adult Patients with Sickle Cell Disease
Chetlapalli K, Butt A, Ito S, Wang D, Calhoun C, Krishnamurti L, Pandya A, Goshua G. Deciding between Multiple Curative Options in Sickle Cell Disease: Cost-Effectiveness of Non-Myeloablative/Reduced Intensity Conditioning Haploidentical Allo-HSCT Vs Gene Therapy Vs Standard of Care in Adult Patients with Sickle Cell Disease. Blood 2024, 144: 601-601. DOI: 10.1182/blood-2024-203234.Peer-Reviewed Original ResearchChronic graft-versus-host diseaseSickle cell diseaseQuality-adjusted life yearsPost-transplant cyclophosphamideReduced intensity conditioningAllo-HSCTGene therapyCurative optionIncremental net monetary benefitProbabilistic sensitivity analysesMyeloablative conditioningHaploidentical donorsCell diseaseAdult patientsExpansion of donor poolUS health system perspectiveCenter for International Blood and Marrow Transplant ResearchGraft-versus-host diseaseEuropean Society for BloodSickle cell disease severityUS commercially insured patientsCost-effective therapeutic optionCost-effectiveness analysisAllo-HSCT outcomesDonor allo-HSCTPeptide 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, PMCID: PMC11564683, 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 therapyA multi‐institutional survey of apheresis services among institutions in the United States
Yurtsever N, Jacobs J, Booth G, Schwartz J, Park Y, Woo J, Lauro D, Torres S, Ward D, Stephens L, Allen E, Tormey C, Adkins B. A multi‐institutional survey of apheresis services among institutions in the United States. Journal Of Clinical Apheresis 2024, 39: e22138. PMID: 38979705, DOI: 10.1002/jca.22138.Peer-Reviewed Original ResearchConceptsTherapeutic plasma exchangeRed blood cell exchangeCell collectionSpectra Optia apheresis systemMulti-institutional surveyHematopoietic progenitor cell collectionProgenitor cell collectionUS academic centersCAR-TPlasma exchangeApheresis therapyGene therapyTransfusion medicine serviceCellular therapyApheresis practiceApheresis systemCell exchangeAcademic medical centerClinical trialsAcademic centersHPC-AApheresisMedical CenterTherapyCoronavirus disease 2019IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10.
Liu J, Jabbari A, Lin C, Akkanapally V, Frankel W, Basu S, He K, Zheng P, Liu Y, Bai X. IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10. The Journal Of Immunology 2024, 213: 559-566. PMID: 38975727, PMCID: PMC11333164, DOI: 10.4049/jimmunol.2400056.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDependovirusDiabetes Mellitus, Type 1DiarrheaForkhead Transcription FactorsGenetic Diseases, X-LinkedGenetic TherapyGerm-Line MutationHumansImmune System DiseasesInterleukin-10Interleukin-27InterleukinsIntestinal DiseasesLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutT-Lymphocytes, RegulatoryConceptsScurfy miceIL-10Gene therapySingle doseGermline mutationsIL-27X-linked (IPEX) syndromeAllogeneic stem cell transplantationInactivating mutationsNaive T cell activationTherapeutic effectRegulatory T cell developmentMutations of FOXP3IL-10 deficiencyRegulatory T cellsStem cell transplantationDownregulation of CD62LT cell activationInduction of IL-10T cell developmentFatal autoimmune diseaseEffector moleculesUpregulation of CD44FOXP3 mutationsIL-10 inductionEfficient editing of the CXCR4 locus using Cas9 ribonucleoprotein complexes stabilized with polyglutamic acid
Golubev D, Komkov D, Shepelev M, Mazurov D, Kruglova N. Efficient editing of the CXCR4 locus using Cas9 ribonucleoprotein complexes stabilized with polyglutamic acid. Доклады Российской Академии Наук Науки О Жизни 2024, 514: 85-90. DOI: 10.31857/s2686738924010164.Peer-Reviewed Original Research
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