ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Optimized lentiviral vector design improves titer and transgene expression of vectors containing the chicken beta-globin locus HS4 insulator element.
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 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, 77 citations in OpenAlex.
- Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.bioRxiv : the preprint server for biology · 2026Article
- Introducing the Stem Cell ASCL2 Reporter STAR into Intestinal Organoids.STAR protocols · 2020Article
- Article
- Development of a laboratory scalable process for enhancing lentivirus production by transient transfection of HEK293 adherent cultures.Gene therapy · 2019Article
- Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector.Molecular therapy. Methods & clinical development · 2017Article
- Assembly PCR synthesis of optimally designed, compact, multi-responsive promoters suited to gene therapy application.Scientific reports · 2016Article
- Insulated Foamy Viral Vectors.Human gene therapy · 2016Article
- Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.Biomedicines · 2016Article
- Current and future alternative therapies for beta-thalassemia major.Biomedical journal · 2016Review
- Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the β(A(T87Q))-Globin Gene.Human gene therapy · 2016Article
- Prevention of Lethal Murine Hypophosphatasia by Neonatal Ex Vivo Gene Therapy Using Lentivirally Transduced Bone Marrow Cells.Human gene therapy · 2015Article
- Progresses towards safe and efficient gene therapy vectors.Oncotarget · 2015Review
- Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β-thalassemia and sickle cell disease.Current gene therapy · 2015Article
- Generation of a lentiviral vector producer cell clone for human Wiskott-Aldrich syndrome gene therapy.Molecular therapy. Methods & clinical development · 2015Article
- Integration-specific In Vitro Evaluation of Lentivirally Transduced Rhesus CD34(+) Cells Correlates With In Vivo Vector Copy Number.Molecular therapy. Nucleic acids · 2013Article
- Comparison of insulators and promoters for expression of the Wiskott-Aldrich syndrome protein using lentiviral vectors.Human gene therapy. Clinical development · 2013Article
- Transient Expression of an LEDGF/p75 Chimera Retargets Lentivector Integration and Functionally Rescues in a Model for X-CGD.Molecular therapy. Nucleic acids · 2013Article
- Biosafety features of lentiviral vectors.Human gene therapy · 2013Review
- Development of gene therapy for thalassemia.Cold Spring Harbor perspectives in medicine · 2012Review
- Recent advances in gene therapy for thalassemia.Journal of pharmacy & bioallied sciences · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Hematopoietic cell gene therapy using retroviral vectors has achieved success in clinical trials. However, safety issues regarding vector insertional mutagenesis have emerged. In two different trials, vector insertion resulted in the transcriptional activation of proto-oncogenes. One strategy for potentially diminishing vector insertional mutagenesis is through the use of self-inactivating lentiviral vectors containing the 1.2-kb insulator element derived from the chicken beta-globin locus. However, use of this element can dramatically decrease both vector titer and transgene expression, thereby compromising its practical use. Here, we studied lentiviral vectors containing either the full-length 1.2-kb insulator or the smaller 0.25-kb core element in both orientations in the partially deleted long-terminal repeat. We show that use of the 0.25-kb core insulator rescued vector titer by alleviating a postentry block to reverse transcription associated with the 1.2-kb element. In addition, in an orientation-dependent manner, the 0.25-kb core element significantly increased transgene expression from an internal promoter due to improved transcriptional termination. This element also demonstrated barrier activity, reducing variability of expression due to position effects. As it is known that the 0.25-kb core insulator has enhancer-blocking activity, this particular insulated lentiviral vector design may be useful for clinical application.
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.