ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Safe and Efficient Gene Therapy for Pyruvate Kinase Deficiency.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2019Trial
- Red lines and green lights: Gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.British journal of haematology · 2026Review
- Review
- Case Report: Successful hematopoietic stem cell transplantation in pediatric pyruvate kinase deficiency: a single-center Asian case series demonstrating favorable outcomes.Frontiers in immunology · 2026Article
- Harnessing DNA barcoding to enhance and sustain polyclonality in gene-edited hematopoietic stem cells.Molecular therapy. Methods & clinical development · 2025Article
- Pyruvate kinase deficiency andHeliyon · 2024Article
- Article
- New Cases and Mutations inInternational journal of molecular sciences · 2023Article
- Review
- Specific correction of pyruvate kinase deficiency-causing point mutations by CRISPR/Cas9 and single-stranded oligodeoxynucleotides.Frontiers in genome editing · 2023Article
- Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency.Blood advances · 2022Article
- Pyruvate Kinase Deficiency: Current Challenges and Future Prospects.Journal of blood medicine · 2022Review
- Gene Editing for Inherited Red Blood Cell Diseases.Frontiers in physiology · 2022Review
- Clinically relevant gene editing in hematopoietic stem cells for the treatment of pyruvate kinase deficiency.Molecular therapy. Methods & clinical development · 2021Article
- Preclinical studies of efficacy thresholds and tolerability of a clinically ready lentiviral vector for pyruvate kinase deficiency treatment.Molecular therapy. Methods & clinical development · 2021Article
- Pyruvate kinase deficiency in children.Pediatric blood & cancer · 2021Article
- Severe Presentation of Congenital Hemolytic Anemias in the Neonatal Age: Diagnostic and Therapeutic Issues.Diagnostics (Basel, Switzerland) · 2021Review
- Gene therapy using haematopoietic stem and progenitor cells.Nature reviews. Genetics · 2021Review
- Targeted Next Generation Sequencing and Diagnosis of Congenital Hemolytic Anemias: A Three Years Experience Monocentric Study.Frontiers in physiology · 2021Article
- The variable manifestations of disease in pyruvate kinase deficiency and their management.Haematologica · 2020Article
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Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pyruvate kinase deficiency (PKD) is a monogenic metabolic disease caused by mutations in the PKLR gene that leads to hemolytic anemia of variable symptomatology and that can be fatal during the neonatal period. PKD recessive inheritance trait and its curative treatment by allogeneic bone marrow transplantation provide an ideal scenario for developing gene therapy approaches. Here, we provide a preclinical gene therapy for PKD based on a lentiviral vector harboring the hPGK eukaryotic promoter that drives the expression of the PKLR cDNA. This therapeutic vector was used to transduce mouse PKD hematopoietic stem cells (HSCs) that were subsequently transplanted into myeloablated PKD mice. Ectopic RPK expression normalized the erythroid compartment correcting the hematological phenotype and reverting organ pathology. Metabolomic studies demonstrated functional correction of the glycolytic pathway in RBCs derived from genetically corrected PKD HSCs, with no metabolic disturbances in leukocytes. The analysis of the lentiviral insertion sites in the genome of transplanted hematopoietic cells demonstrated no evidence of genotoxicity in any of the transplanted animals. Overall, our results underscore the therapeutic potential of the hPGK-coRPK lentiviral vector and provide high expectations toward the gene therapy of PKD and other erythroid metabolic genetic disorders.
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