ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
A microRNA-regulated and GP64-pseudotyped lentiviral vector mediates stable expression of FVIII in a murine model of Hemophilia A.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 72 citations in OpenAlex.
- Deaths in gene therapy of Duchenne muscular dystrophy and other diseases: Underlying mechanisms and mitigating strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Delivering genes with human immunodeficiency virus-derived vehicles: still state-of-the-art after 25 years.Journal of biomedical science · 2022Review
- Liver-directed lentiviral gene therapy corrects hemophilia A mice and achieves normal-range factor VIII activity in non-human primates.Nature communications · 2022Article
- Review
- The Possible Non-Mutational Causes of FVIII Deficiency: Non-Coding RNAs and Acquired Hemophilia A.Frontiers in medicine · 2021Review
- Correction of bleeding in experimental severe hemophilia A by systemic delivery of factor VIII-encoding mRNA.Haematologica · 2020Article
- The Immune Response to the fVIII Gene Therapy in Preclinical Models.Frontiers in immunology · 2020Review
- Modulation of immune responses in lentiviral vector-mediated gene transfer.Cellular immunology · 2019Review
- Transcriptional Targeting and MicroRNA Regulation of Lentiviral Vectors.Molecular therapy. Methods & clinical development · 2019Review
- Lessons learned from lung and liver in-vivo gene therapy: implications for the future.Expert opinion on biological therapy · 2018Review
- Large-scale production of lentiviral vectors using multilayer cell factories.Journal of biological methods · 2018Article
- Platelet Gene Therapy Promotes Targeted Peripheral Tolerance by Clonal Deletion and Induction of Antigen-Specific Regulatory T Cells.Frontiers in immunology · 2018Article
- Immune tolerance induced by platelet-targeted factor VIII gene therapy in hemophilia A mice is CD4 T cell mediated.Journal of thrombosis and haemostasis : JTH · 2017Article
- A Novel Platform for Immune Tolerance Induction in Hemophilia A Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Toward Personalized Gene Therapy: Characterizing the Host Genetic Control of Lentiviral-Vector-Mediated Hepatic Gene Delivery.Molecular therapy. Methods & clinical development · 2017Article
- Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A.Frontiers in immunology · 2017Review
- In Vivo Gene Delivery to Lymph Node Stromal Cells Leads to Transgene-specific CD8+ T Cell Anergy in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- MicroRNA-regulated viral vectors for gene therapy.World journal of experimental medicine · 2016Review
- MicroRNA in atherothromobosis: is it useful as a disease marker?Thrombosis journal · 2016Review
- Liver-directed lentiviral gene therapy in a dog model of hemophilia B.Science translational medicine · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The objective to use gene therapy to provide sustained, therapeutic levels of factor VIII (FVIII) for hemophilia A is compromised by the emergence of inhibitory antibodies that prevent FVIII from performing its essential function as a cofactor for factor IX (FIX). FVIII appears to be more immunogenic than FIX and an immune response is associated more frequently with FVIII than FIX gene therapy strategies. We have evaluated a modified lentiviral delivery strategy that facilitates liver-restricted transgene expression and prevents off-target expression in hematopoietic cells by incorporating microRNA (miRNA) target sequences. In contrast to outcomes using this strategy to deliver FIX, this modified delivery strategy was in and of itself insufficient to prevent an anti-FVIII immune response in treated hemophilia A mice. However, pseudotyping the lentivirus with the GP64 envelope glycoprotein, in conjunction with a liver-restricted promoter and a miRNA-regulated FVIII transgene resulted in sustained, therapeutic levels of FVIII. These modifications to the lentiviral delivery system effectively restricted FVIII transgene expression to the liver. Plasma levels of FVIII could be increased to around 9% that of normal levels when macrophages were depleted prior to treating the hemophilia A mice with the modified lentiviral FVIII delivery system.
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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.