ArticleProceedings of the National Academy of Sciences of the United States of America2009
Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 52 citations in OpenAlex.
- MPSI Manifestations and Treatment Outcome: Skeletal Focus.International journal of molecular sciences · 2022Review
- Delivering gene therapy for mucopolysaccharide diseases.Frontiers in molecular biosciences · 2022Review
- New function of a well-known promoter: Enhancer activity of minimal CMV promoter enables efficient dual-cassette transgene expression.The journal of gene medicine · 2021Article
- Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement.Biomolecules · 2021Review
- miR-143 Regulates Lysosomal Enzyme Transport across the Blood-Brain Barrier and Transforms CNS Treatment for Mucopolysaccharidosis Type I.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Lentiviral Hematopoietic Stem Cell Gene Therapy Rescues Clinical Phenotypes in a Murine Model of Pompe Disease.Molecular therapy. Methods & clinical development · 2020Article
- Intravenous delivery for treatment of mucopolysaccharidosis type I: A comparison of AAV serotypes 9 and rh10.Molecular genetics and metabolism reports · 2020Article
- Ex vivo editing of human hematopoietic stem cells for erythroid expression of therapeutic proteins.Nature communications · 2020Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I.Nature communications · 2019Article
- Review
- Getting the Most: Enhancing Efficacy by Promoting Erythropoiesis and Thrombopoiesis after Gene Therapy in Mice with Hurler Syndrome.Molecular therapy. Methods & clinical development · 2018Article
- Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches.Italian journal of pediatrics · 2018Review
- Comprehensive evaluation of blood-brain barrier-forming micro-vasculatures: Reference and marker genes with cellular composition.PloS one · 2018Article
- Liver-Directed Human Amniotic Epithelial Cell Transplantation Improves Systemic Disease Phenotype in Hurler Syndrome Mouse Model.Stem cells translational medicine · 2017Article
- Article
- Hematopoietic Stem Cell Gene Therapy for Storage Disease: Current and New Indications.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Neonatal cellular and gene therapies for mucopolysaccharidoses: the earlier the better?Journal of inherited metabolic disease · 2016Review
- Progression of Behavioral and CNS Deficits in a Viable Murine Model of Chronic Neuronopathic Gaucher Disease.PloS one · 2016Article
- Gene therapy for neurologic manifestations of mucopolysaccharidoses.Expert opinion on drug delivery · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Restricting transgene expression to maturing erythroid cells can reduce the risk for activating oncogenes in hematopoietic stem cells (HSCs) and their progeny, yet take advantage of their robust protein synthesis machinery for high-level protein production. This study sought to evaluate the feasibility and efficacy of reprogramming erythroid cells for production of a lysosomal enzyme, alpha-L-iduronidase (IDUA). An erythroid-specific hybrid promoter provided inducible IDUA expression and release during in vitro erythroid differentiation in murine erythroleukemia cells, resulting in phenotypical cross-correction in an enzyme-deficient lymphoblastoid cell line derived from patients with mucopolysaccharidosis type I (MPS I). Stable and higher than normal plasma IDUA levels were achieved in vivo in primary and secondary MPS I chimeras for at least 9 months after transplantation of HSCs transduced with the erythroid-specific IDUA-containing lentiviral vector (LV). Moreover, long-term metabolic correction was demonstrated by normalized urinary glycosaminoglycan accumulation in all treated MPS I mice. Complete normalization of tissue pathology was observed in heart, liver, and spleen. Notably, neurological function and brain pathology were significantly improved in MPS I mice by erythroid-derived, higher than normal peripheral IDUA protein. These data demonstrate that late-stage erythroid cells, transduced with a tissue-specific LV, can deliver a lysosomal enzyme continuously at supraphysiological levels to the bloodstream and can correct the disease phenotype in both viscera and CNS of MPS I mice. This approach provides a paradigm for the utilization of RBC precursors as a depot for efficient and potentially safer systemic delivery of nonsecreted proteins by ex vivo HSC gene transfer.
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