ArticleMolecular therapy : the journal of the American Society of Gene Therapy2008
Erythroid-specific human factor IX delivery from in vivo selected hematopoietic stem cells following nonmyeloablative conditioning in hemophilia B mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Red blood cells in biology and translational medicine: natural vehicle inspires new biomedical applications.Theranostics · 2024Review
- The intersection of vector biology, gene therapy, and hemophilia.Research and practice in thrombosis and haemostasis · 2021Review
- Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.Blood advances · 2021Article
- Ex vivo editing of human hematopoietic stem cells for erythroid expression of therapeutic proteins.Nature communications · 2020Article
- Long-Term Persistence of Anti-HIV Broadly Neutralizing Antibody-Secreting Hematopoietic Cells in Humanized Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects.Journal of inherited metabolic disease · 2017Review
- Towards in vivo amplification: Overcoming hurdles in the use of hematopoietic stem cells in transplantation and gene therapy.World journal of stem cells · 2015Review
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- Development of Gene Transfer for Induction of Antigen-specific Tolerance.Molecular therapy. Methods & clinical development · 2014Article
- Role of antigen-specific regulatory CD4+CD25+ T cells in tolerance induction after neonatal IP administration of AAV-hF.IX.Gene therapy · 2013Article
- Ex-vivo expansion of red blood cells: how real for transfusion in humans?Blood reviews · 2012Review
- Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation.British journal of haematology · 2012Review
- Cell- and gene-based therapeutic approaches for neurological deficits in mucopolysaccharidoses.Current pharmaceutical biotechnology · 2011Review
- Platelets as delivery systems for disease treatments.Advanced drug delivery reviews · 2010Review
- Article
- Supplying clotting factors from hematopoietic stem cell-derived erythroid and megakaryocytic lineage cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Review
- Independent and high-level dual-gene expression in adult stem-progenitor cells from a single lentiviral vector.Gene therapy · 2009Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have developed a lentiviral vector system for human factor IX (hFIX) gene transfer in hematopoietic stem cells (HSCs) that provides erythroid cell-derived systemic protein delivery following nonmyeloablative conditioning and in vivo methylguanine methyltransferase (MGMT) drug selection. After bone marrow transplantation under moderate Busulfan conditioning, the initial hFIX expression in the chimeras was minimally detectable. However, the hFIX levels rose sharply following in vivo MGMT-drug selection and eventually reached a level that is considered curative in hemophilia B therapy (>500 ng/ml). The rise of hFIX levels was proportional to the increase in vector copy (VC) number in peripheral blood cells. High levels of hFIX expression were maintained in serially engrafted mice chimeras for 18 months. Importantly, high-level hFIX expression by erythroid cells did not result in anemia or adversely affect red blood cell counts. The prospect of combining reduced intensity conditioning, a presumably lowered risk of insertional mutagenesis due to low VC number requirement and erythroid-restricted transgene expression, as well as long-term protein expression at high level, strongly supports the potential applicability of adult stem cell-based gene therapy in nonlethal blood or metabolic disorders, as demonstrated here for hemophilia.
Indexed as
Identifiers
What OpenQuestion holds
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.