ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Rescue of pyruvate kinase deficiency in mice by gene therapy using the human isoenzyme.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 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
- From Mutation to Manifestation: Evaluation of aAnimals : an open access journal from MDPI · 2025Article
- Fetal gene therapy.Journal of inherited metabolic disease · 2024Review
- Pyruvate kinase activators for treatment of pyruvate kinase deficiency.Hematology. American Society of Hematology. Education Program · 2023Article
- Updates and advances in pyruvate kinase deficiency.Trends in molecular medicine · 2023Review
- Catching Them Early: Framework Parameters and Progress for Prenatal and Childhood Application of Advanced Therapies.Pharmaceutics · 2022Review
- Preclinical studies of efficacy thresholds and tolerability of a clinically ready lentiviral vector for pyruvate kinase deficiency treatment.Molecular therapy. Methods & clinical development · 2021Article
- Clinically relevant gene editing in hematopoietic stem cells for the treatment of pyruvate kinase deficiency.Molecular therapy. Methods & clinical development · 2021Article
- Pyruvate kinase deficiency in children.Pediatric blood & cancer · 2021Article
- Molecular heterogeneity of pyruvate kinase deficiency.Haematologica · 2020Review
- AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency.Blood · 2017Article
- Safe and Efficient Gene Therapy for Pyruvate Kinase Deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Next generation research and therapy in red blood cell diseases.Haematologica · 2016Article
- Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells.Stem cell reports · 2015Article
- Prevention of Lethal Murine Hypophosphatasia by Neonatal Ex Vivo Gene Therapy Using Lentivirally Transduced Bone Marrow Cells.Human gene therapy · 2015Article
- Anemia: progress in molecular mechanisms and therapies.Nature medicine · 2015Review
- Reticulocyte-prone malaria parasites predominantly invade CD71hi immature cells: implications for the development of an in vitro culture for Plasmodium vivax.Malaria journal · 2013Article
- Stem cell selection in vivo using foamy vectors cures canine pyruvate kinase deficiency.PloS one · 2012Article
- A mouse model of in utero transplantation.Journal of visualized experiments : JoVE · 2011Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human erythrocyte R-type pyruvate kinase deficiency (PKD) is a disorder caused by mutations in the PKLR gene that produces chronic nonspherocytic hemolytic anemia. Besides periodic blood transfusion and splenectomy, severe cases require bone marrow (BM) transplant, which makes this disease a good candidate for gene therapy. Here, the normal human R-type pyruvate kinase (hRPK) complementary (cDNA) was expressed in hematopoietic stem cells (HSCs) derived from pklr deficient mice, using a retroviral vector system. These mice show a similar red blood cell phenotype to that observed in human PKD. Transduced HSCs were transplanted into myeloablated adult PKD mice or in utero injected into nonconditioned PKD fetuses. In the myeloablated recipients, the hematological manifestations of PKD were completely resolved and normal percentages of late erythroid progenitors, reticulocyte and erythrocyte counts, hemoglobin levels and erythrocyte biochemistry were restored. Corrected cells preserved their rescuing capacity after secondary and tertiary transplant. When corrected cells were in utero transplanted, partial correction of the erythrocyte disease was obtained, although a very low number of corrected cells became engrafted, suggesting a different efficiency of cell therapy applied in utero. Our data suggest that transduction of human RPK cDNA in PKLR mutated HSCs could be an effective strategy in severe cases of PKD.
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