ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Cyclosporin a and rapamycin relieve distinct lentiviral restriction blocks in hematopoietic stem and progenitor cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 55 citations in OpenAlex.
- Expanding the frontier of CAR therapy: comparative insights into CAR-T, CAR-NK, CAR-M, and CAR-DC approaches.Annals of hematology · 2025Review
- Advancements in Hematopoietic Stem Cell Gene Therapy: A Journey of Progress for Viral Transduction.Cells · 2024Review
- Removal of innate immune barriers allows efficient transduction of quiescent human hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- CAR Gene Delivery by T-cell Targeted Lentiviral Vectors is Enhanced by Rapamycin Induced Reduction of Antiviral Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Interferon-inducible phospholipids govern IFITM3-dependent endosomal antiviral immunity.The EMBO journal · 2023Article
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- Current approaches and potential challenges in the delivery of gene editing cargos into hematopoietic stem and progenitor cells.Frontiers in genome editing · 2023Review
- Improved alpharetrovirus-based Gag.MS2 particles for efficient and transient delivery of CRISPR-Cas9 into target cells.Molecular therapy. Nucleic acids · 2022Article
- Article
- HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules.Retrovirology · 2021Review
- Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy.Journal of hematology & oncology · 2021Review
- Antiviral immunity and nucleic acid sensing in haematopoietic stem cell gene engineering.Gene therapy · 2021Review
- CAR-NK Cells: From Natural Basis to Design for Kill.Frontiers in immunology · 2021Review
- Optimizing lentiviral vector transduction of hematopoietic stem cells for gene therapy.Gene therapy · 2020Article
- Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side.Pharmaceutics · 2020Review
- Rosuvastatin Enhances VSV-G Lentiviral Transduction of NK Cells via Upregulation of the Low-Density Lipoprotein Receptor.Molecular therapy. Methods & clinical development · 2020Article
- Assessment and streamlined preparation of low-cytotoxicity lentiviral vectors for mobilized human hematopoietic stem cell transduction.Experimental hematology · 2020Article
- Mouse models in hematopoietic stem cell gene therapy and genome editing.Biochemical pharmacology · 2020Review
- Successfully transfected primary peripherally mobilized human CD34+ hematopoietic stem and progenitor cells (HSPCs) demonstrate increased susceptibility to retroviral infection.Virology journal · 2020Article
- Cyclosporine H Improves the Multi-Vector Lentiviral Transduction of Murine Haematopoietic Progenitors and Stem Cells.Scientific reports · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Improving hematopoietic stem and progenitor cell (HSPC) permissiveness to HIV-derived lentiviral vectors (LVs) remains a challenge for the field of gene therapy as high vector doses and prolonged ex vivo culture are still required to achieve clinically relevant transduction levels. We report here that Cyclosporin A (CsA) and Rapamycin (Rapa) significantly improve LV gene transfer in human and murine HSPC. Both compounds increased LV but not gammaretroviral transduction and acted independently of calcineurin and autophagy. Improved gene transfer was achieved across all CD34(+) subpopulations, including in long-term SCID repopulating cells. Effects of CsA were specific of HSPC and opposite to its known impact on HIV replication. Mutating the Cyclophilin A binding pocket of the viral capsid (CA) further improved transduction in combination with CsA. Tracking of the LV genome fate revealed that CsA relieves a CA-dependent early block and increases integration, while Rapa acts early in LV infection independently of the viral CA. In agreement, only Rapa was able to improve transduction by an integrase-defective LV harboring wild-type CA. Overall, our findings pave the way for more efficient and sustainable LV gene therapy in human HSPCs and shed light on the multiple innate barriers specifically hampering LV transduction in these cells.
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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.