ArticleMolecular therapy. Methods & clinical development2015
Design of a regulated lentiviral vector for hematopoietic stem cell gene therapy of globoid cell leukodystrophy.
Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Development of a Lentiviral Vector for High-Yield Production of Synthetic and Recombinant GCase for Gaucher Disease Therapy.International journal of molecular sciences · 2025Article
- Therapeutic efficacy of intracerebral hematopoietic stem cell gene therapy in an Alzheimer's disease mouse model.Nature communications · 2024Article
- An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Gene and Cellular Therapies for Leukodystrophies.Pharmaceutics · 2023Review
- Promoter considerations in the design of lentiviral vectors for use in treating lysosomal storage diseases.Molecular therapy. Methods & clinical development · 2022Review
- CRISPR Editing Enables Consequential Tag-Activated MicroRNA-Mediated Endogene Deactivation.International journal of molecular sciences · 2022Article
- Human iPSC-derived astrocytes generated from donors with globoid cell leukodystrophy display phenotypes associated with disease.PloS one · 2022Article
- Storage of Mutant Human SOD1 in Non-Neural Cells from the Type-1 Amyotrophic Lateral Sclerosis ratBiomedicines · 2021Article
- Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes.Stem cell reports · 2021Article
- Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies.Frontiers in cellular neuroscience · 2021Review
- Harnessing the Potential of Stem Cells for Disease Modeling: Progress and Promises.Journal of personalized medicine · 2020Review
- Article
- Insight into Mechanobiology: How Stem Cells Feel Mechanical Forces and Orchestrate Biological Functions.International journal of molecular sciences · 2019Review
- The IS2 Element Improves Transcription Efficiency of Integration-Deficient Lentiviral Vector Episomes.Molecular therapy. Nucleic acids · 2018Article
- Adipose Stem Cell Translational Applications: From Bench-to-Bedside.International journal of molecular sciences · 2018Review
- Review
- Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34Molecular therapy. Methods & clinical development · 2017Article
- Quantum dots and potential therapy for Krabbe's disease.Journal of neuroscience research · 2016Review
- Hematopoietic Stem cell transplantation and lentiviral vector-based gene therapy for Krabbe's disease: Present convictions and future prospects.Journal of neuroscience research · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Globoid cell leukodystrophy (GLD) is a demyelinating lysosomal storage disease due to the deficiency of the galactocerebrosidase (GALC) enzyme. The favorable outcome of hematopoietic stem and progenitor cell (HSPC)-based approaches in GLD and other similar diseases suggests HSPC gene therapy as a promising therapeutic option for patients. The path to clinical development of this strategy was hampered by a selective toxicity of the overexpressed GALC in the HSPC compartment. Here, we presented the optimization of a lentiviral vector (LV) in which miR-126 regulation was coupled to codon optimization of the human GALC cDNA to obtain a selective and enhanced enzymatic activity only upon transduced HSPCs differentiation. The safety of human GALC overexpression driven by this LV was extensively demonstrated in vitro and in vivo on human HSPCs from healthy donors. No perturbation in the content of proapoptotic sphingolipids, gene expression profile, and capability of engraftment and mutlilineage differentiation in chimeric mice was observed. The therapeutic potential of this LV was then assessed in a severe GLD murine model that benefited from transplantation of corrected HSPCs with longer survival and ameliorated phenotype as compared to untreated siblings. This construct has thus been selected as a candidate for clinical translation.
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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.