ArticleAmerican journal of hematology2016
Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease.
Article in American journal of hematology, 2016. 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, 28 citations in OpenAlex.
- In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation.Blood advances · 2024Trial
- Post-Transcriptional Genetic Silencing ofThe New England journal of medicine · 2021Trial
- Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease.Cell stem cell · 2026Article
- Mathematical modeling of SCD: a literature review.Journal of sickle cell disease · 2025Review
- Long live the red blood cell: biotin tagging in SCD.Blood advances · 2024Article
- A systems pharmacology model for gene therapy in sickle cell disease.CPT: pharmacometrics & systems pharmacology · 2021Article
- Genetic therapies for the first molecular disease.The Journal of clinical investigation · 2021Review
- Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy.Molecular therapy. Methods & clinical development · 2020Article
- Article
- Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype.Science advances · 2020Article
- Genome editing of HBG1 and HBG2 to induce fetal hemoglobin.Blood advances · 2019Article
- New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling.Seminars in cancer biology · 2019Review
- An Optimized Lentiviral Vector Efficiently Corrects the Human Sickle Cell Disease Phenotype.Molecular therapy. Methods & clinical development · 2018Article
- Replicative cellular age distributions in compartmentalized tissues.Journal of the Royal Society, Interface · 2018Article
- At least 20% donor myeloid chimerism is necessary to reverse the sickle phenotype after allogeneic HSCT.Blood · 2017Article
- Extinction rates in tumour public goods games.Journal of the Royal Society, Interface · 2017Article
- Gene Therapy for β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Long-Term Engraftment and Fetal Globin Induction uponMolecular therapy. Methods & clinical development · 2017Article
- Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype.The Journal of clinical investigation · 2016Article
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
Recent advances in gene therapy and genome-engineering technologies offer the opportunity to correct sickle cell disease (SCD), a heritable disorder caused by a point mutation in the β-globin gene. The developmental switch from fetal γ-globin to adult β-globin is governed in part by the transcription factor (TF) BCL11A. This TF has been proposed as a therapeutic target for reactivation of γ-globin and concomitant reduction of β-sickle globin. In this and other approaches, genetic alteration of a portion of the hematopoietic stem cell (HSC) compartment leads to a mixture of sickling and corrected red blood cells (RBCs) in periphery. To reverse the sickling phenotype, a certain proportion of corrected RBCs is necessary; the degree of HSC alteration required to achieve a desired fraction of corrected RBCs remains unknown. To address this issue, we developed a mathematical model describing aging and survival of sickle-susceptible and normal RBCs; the former can have a selective survival advantage leading to their overrepresentation. We identified the level of bone marrow chimerism required for successful stem cell-based gene therapies in SCD. Our findings were further informed using an experimental mouse model, where we transplanted mixtures of Berkeley SCD and normal murine bone marrow cells to establish chimeric grafts in murine hosts. Our integrative theoretical and experimental approach identifies the target frequency of HSC alterations required for effective treatment of sickling syndromes in humans. Our work replaces episodic observations of such target frequencies with a mathematical modeling framework that covers a large and continuous spectrum of chimerism conditions. Am. J. Hematol. 91:931-937, 2016. © 2016 Wiley Periodicals, Inc.
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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.