ArticleGene therapy2013
Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.
Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Antimetabolites synergize with non-genotoxic antibody drug conjugate conditioning in hematopoietic stem cell lentiviral gene therapy.Molecular therapy. Advances · 2026Article
- Combination gene therapy with AAV based RPE65 and survivin vectors sustains phenotypic rescue in neural retina of LCA2 mice.Molecular and cellular biochemistry · 2026Article
- Comparison of different gene addition strategies to modify placental derived-mesenchymal stromal cells to produce FVIII.Frontiers in immunology · 2022Article
- Non-genotoxic conditioning facilitates hematopoietic stem cell gene therapy for hemophilia A using bioengineered factor VIII.Molecular therapy. Methods & clinical development · 2021Article
- Investigating Optimal Autologous Cellular Platforms for Prenatal or Perinatal Factor VIII Delivery to Treat Hemophilia A.Frontiers in cell and developmental biology · 2021Article
- Lentiviral Gene Therapy for Familial Hemophagocytic Lymphohistiocytosis Type 3, Caused byHuman gene therapy · 2020Article
- The Immune Response to the fVIII Gene Therapy in Preclinical Models.Frontiers in immunology · 2020Review
- Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A.Current stem cell reports · 2019Article
- Production of Therapeutic Enzymes by Lentivirus Transgenesis.Advances in experimental medicine and biology · 2019Review
- Improvement of K562 Cell Line Transduction by FBS Mediated Attachment to the Cell Culture Plate.BioMed research international · 2019Article
- Preclinical Development of a Hematopoietic Stem and Progenitor Cell Bioengineered Factor VIII Lentiviral Vector Gene Therapy for Hemophilia A.Human gene therapy · 2018Article
- Target-Cell-Directed Bioengineering Approaches for Gene Therapy of Hemophilia A.Molecular therapy. Methods & clinical development · 2018Article
- In Utero Transplantation of Placenta-Derived Mesenchymal Stromal Cells for Potential Fetal Treatment of Hemophilia A.Cell transplantation · 2018Article
- Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Review
- Progresses towards safe and efficient gene therapy vectors.Oncotarget · 2015Review
- Re-expression of LKB1 in LKB1-mutant EKVX cells leads to resistance to paclitaxel through the up-regulation of MDR1 expression.Lung cancer (Amsterdam, Netherlands) · 2015Article
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- High-throughput screening identifies compounds that enhance lentiviral transduction.Gene therapy · 2014Article
- Simplified prototyping of perfusable polystyrene microfluidics.Biomicrofluidics · 2014Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fVIII. The bioengineered construct then was used effectively to treat knockout mice with hemophilia A. In the current study, we focused on optimizing self-inactivating (SIN) lentiviral vector systems by analyzing the efficacy of various lentiviral components in terms of virus production, transduction efficiency and transgene expression. Specifically, three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3) various internal promoters. The inclusion of a WPRE sequence had negligible effects on viral production and HP-fVIII expression. HIV and SIV vectors were compared and found to be similar with respect to transduction efficiency in both K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII by the SIV system, which was evident in both K562 and BHK-M cell lines. To further compare expression of HP-fVIII from an SIV-based lentiviral system, we constructed expression vectors containing the high expression transgene and a human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase promoter. Expression was significantly greater from the CMV promoter, which also yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these studies, an optimized vector contains the HP-fVIII transgene driven by a CMV internal promoter within a SIV-based lentiviral backbone lacking a WPRE.
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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.