ArticleBlood2009
A novel human gamma-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 112 citations in OpenAlex.
- Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.Nature medicine · 2025Trial
- Advances in Gene Therapy for Inherited Haemoglobinopathies.Hematology reports · 2025Review
- Gene therapy for hemoglobinopathies: Clinical trial results and biology of hematopoietic stem cell and the bone marrow niche.Cell reports. Medicine · 2025Review
- Gene Therapy of Beta Hemoglobinopathies.Biomedicines · 2025Review
- Article
- Preclinical efficacy of a modified gamma-globin lentivirus gene therapy in Berkeley sickle cell anemia mice and human xenograft models.Molecular therapy. Methods & clinical development · 2025Article
- Clinical hematopoietic stem cell-based gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Current and future treatments for sickle cell disease: From hematopoietic stem cell transplantation to in vivo gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Article
- PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease.Science advances · 2024Article
- Review
- Article
- Precision Editing as a Therapeutic Approach for β-Hemoglobinopathies.International journal of molecular sciences · 2023Review
- Review
- Diverse Approaches to Gene Therapy of Sickle Cell Disease.Annual review of medicine · 2023Review
- Stem Cell-Based Therapeutic Approaches in Genetic Diseases.Advances in experimental medicine and biology · 2023Article
- The Optimized γ-Globin Lentiviral Vector GGHI-mB-3D Leads to Nearly Therapeutic HbF Levels In Vitro in CD34Viruses · 2022Article
- In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies.JCI insight · 2022Article
- Limitations of mouse models for sickle cell disease conferred by their human globin transgene configurations.Disease models & mechanisms · 2022Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
We show that lentiviral delivery of human gamma-globin gene under beta-globin regulatory control elements in hematopoietic stem cells (HSCs) results in sufficient postnatal fetal hemoglobin (HbF) expression to correct sickle cell anemia (SCA) in the Berkeley "humanized" sickle mouse. Upon de-escalating the amount of transduced HSCs in transplant recipients, using reduced-intensity conditioning and varying gene transfer efficiency and vector copy number, we assessed critical parameters needed for correction. A systematic quantification of functional and hematologic red blood cell (RBC) indices, organ pathology, and life span was used to determine the minimal amount of HbF, F cells, HbF/F-cell, and gene-modified HSCs required for correcting the sickle phenotype. We show that long-term amelioration of disease occurred (1) when HbF exceeded 10%, F cells constituted two-thirds of the circulating RBCs, and HbF/F cell was one-third of the total hemoglobin in sickle RBCs; and (2) when approximately 20% gene-modified HSCs repopulated the marrow. Moreover, we show a novel model using reduced-intensity conditioning to determine genetically corrected HSC threshold that corrects a hematopoietic disease. These studies provide a strong preclinical model for what it would take to genetically correct SCA and are a foundation for the use of this vector in a human clinical trial.
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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.