ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Integration-deficient lentiviral vectors expressing codon-optimized R338L human FIX restore normal hemostasis in Hemophilia B mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Trial
- Application Advances of Lentiviral Vectors: From Gene Therapy to Vaccine Development.Molecular biotechnology · 2026Review
- The Template-Jumping Editing Approach inInternational journal of molecular sciences · 2025Article
- Analysis of Hepatic Lentiviral Vector Transduction: Implications for Preclinical Studies and Clinical Gene Therapy Protocols.Viruses · 2025Article
- Rewriting the script: gene therapy and genome editing for von Willebrand Disease.Frontiers in genome editing · 2025Review
- Analysis of hepatic lentiviral vector transduction; implications for preclinical studies and clinical gene therapy protocols.bioRxiv : the preprint server for biology · 2024Article
- Viral and Non-Viral Systems to Deliver Gene Therapeutics to Clinical Targets.International journal of molecular sciences · 2024Review
- Article
- Gene editing monkeys: Retrospect and outlook.Frontiers in cell and developmental biology · 2022Review
- Inadvertent Transfer of Murine VL30 Retrotransposons to CAR-T Cells.Advances in cell and gene therapy · 2022Article
- Improved Functionality of Integration-Deficient Lentiviral Vectors (IDLVs) by the Inclusion of ISPharmaceutics · 2021Article
- Evolutionary insights into coagulation factor IX Padua and other high-specific-activity variants.Blood advances · 2021Article
- Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders.Open life sciences · 2021Review
- Review
- Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness.Frontiers in molecular neuroscience · 2020Article
- Ribosome profiling of HEK293T cells overexpressing codon optimized coagulation factor IX.F1000Research · 2020Article
- Enhanced Factor IX Activity following Administration of AAV5-R338L "Padua" Factor IX versus AAV5 WT Human Factor IX in NHPs.Molecular therapy. Methods & clinical development · 2019Article
- A Single Synonymous Variant (c.354G>A [p.P118P]) inInternational journal of molecular sciences · 2019Article
- Effects of codon optimization on coagulation factor IX translation and structure: Implications for protein and gene therapies.Scientific reports · 2019Article
- Epilepsy Gene Therapy Using an Engineered Potassium Channel.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Integration-deficient lentiviral vectors (IDLVs) have been shown to transduce a wide spectrum of target cells and organs in vitro and in vivo and to maintain long-term transgene expression in nondividing cells. However, epigenetic silencing of episomal vector genomes reduces IDLV transgene expression levels and renders these safe vectors less efficient. In this article, we describe for the first time a complete correction of factor IX (FIX) deficiency in hemophilia B mice by IDLVs carrying a novel, highly potent human FIX cDNA. A 50-fold increase in human FIX cDNA potency was achieved by combining two mechanistically independent yet synergistic strategies: (i) optimization of the human FIX cDNA codon usage to increase human FIX protein production per vector genome and (ii) generation of a highly catalytic mutant human FIX protein in which the arginine residue at position 338 was substituted with leucine. The enhanced human FIX activity was not associated with liver damage or with the formation of human FIX-directed inhibitory antibodies and rendered IDLV-treated FIX-knockout mice resistant to a challenging tail-clipping assay. A novel S1 nuclease-based B1-quantitative polymerase chain reaction assay showed low levels of IDLV integration in mouse liver. Overall, this study demonstrates that IDLVs carrying an improved human FIX cDNA safely and efficiently cure hemophilia B in a mouse model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.