ArticleStem cells (Dayton, Ohio)2008
Combinatorial incorporation of enhancer-blocking components of the chicken beta-globin 5'HS4 and human T-cell receptor alpha/delta BEAD-1 insulators in self-inactivating retroviral vectors reduces their genotoxic potential.
Article in Stem cells (Dayton, Ohio), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 65 citations in OpenAlex.
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- Current landscape of vector safety and genotoxicity after hematopoietic stem or immune cell gene therapy.Leukemia · 2025Review
- Advancements inMolecules (Basel, Switzerland) · 2024Review
- Mechanisms and Delivery of tRNA Therapeutics.Chemical reviews · 2024Review
- Quantitative spatial and temporal assessment of regulatory element activity in zebrafish.eLife · 2021Article
- Coordinated β-globin expression and α2-globin reduction in a multiplex lentiviral gene therapy vector for β-thalassemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Viral vector platforms within the gene therapy landscape.Signal transduction and targeted therapy · 2021Review
- A Small Key for a Heavy Door: Genetic Therapies for the Treatment of Hemoglobinopathies.Frontiers in genome editing · 2020Review
- Engineering Globin Gene Expression.Molecular therapy. Methods & clinical development · 2019Review
- Gene Therapy for Hemoglobinopathies.Human gene therapy · 2018Review
- Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned.Cell stem cell · 2017Review
- Evidence for the in vivo safety of insulated foamy viral vectors.Gene therapy · 2017Article
- Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives.Journal of translational medicine · 2016Review
- Insulated Foamy Viral Vectors.Human gene therapy · 2016Article
- Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.Blood · 2016Review
- Gene therapy for hemoglobin disorders - a mini-review.Journal of rare diseases research & treatment · 2016Article
- Potentially therapeutic levels of anti-sickling globin gene expression following lentivirus-mediated gene transfer in sickle cell disease bone marrow CD34+ cells.Experimental hematology · 2015Article
- The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.Molecular therapy. Methods & clinical development · 2015Article
- Uncovering and dissecting the genotoxicity of self-inactivating lentiviral vectors in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Design and Potential of Non-Integrating Lentiviral Vectors.Biomedicines · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Insertional mutagenesis by retroviral vectors has emerged as a serious impediment to the widespread application of hematopoietic stem cell gene transfer for the treatment of hematologic diseases. Here we report the development of a 77-base pair element, FII/BEAD-A (FB), which contains the minimal enhancer-blocking components of the chicken beta-globin 5'HS4 insulator and a homologous region from the human T-cell receptor alpha/delta BEAD-1 insulator. With a new flow cytometry-based assay, we show that the FB element is as effective in enhancer-blocking activity as the prototypical 1.2-kilobase 5'HS4 insulator fragment. When incorporated into the residual U3 region of the 3' long terminal repeat (LTR) of a self-inactivating (SIN) gammaretroviral vector, the FB element was stably transferred to the 5' LTR during reverse transcription, flanking the integrated transgene expression cassette. Notably, using a recently established in vitro insertional mutagenesis assay involving primary murine hematopoietic cells, we found that SIN gammaretroviral vectors, as well as SIN lentiviral vectors, containing the FB element exhibited greatly reduced transforming potential-to background levels under the experimental conditions used-compared with their unshielded counterparts. These results suggest that the FB element-mediated enhancer-blocking modification is a promising approach to dramatically improve the safety of retroviral vectors for therapeutic gene transfer.
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.