ArticleHuman gene therapy2010
Modification of integration site preferences of an HIV-1-based vector by expression of a novel synthetic protein.
Article in Human gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 71 citations in OpenAlex.
- Relationship between the distribution of LEDGF along genes and positions of HIV-1 DNA integration.mBio · 2026Article
- Review
- Delivering genes with human immunodeficiency virus-derived vehicles: still state-of-the-art after 25 years.Journal of biomedical science · 2022Review
- Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges.Frontiers in molecular biosciences · 2021Review
- Efficient Nuclease-Directed Integration of Lentivirus Vectors into the Human Ribosomal DNA Locus.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Cellular and molecular mechanisms of HIV-1 integration targeting.Cellular and molecular life sciences : CMLS · 2018Review
- Accumulation of long-term transcriptionally active integrated retroviral vectors in active promoters and enhancers.Nucleic acids research · 2017Article
- Integration site selection by retroviruses and transposable elements in eukaryotes.Nature reviews. Genetics · 2017Review
- Retroviral DNA Integration.Chemical reviews · 2016Review
- Comparative Analysis of HIV-1 and Murine Leukemia Virus Three-Dimensional Nuclear Distributions.Journal of virology · 2016Article
- What Integration Sites Tell Us about HIV Persistence.Cell host & microbe · 2016Review
- Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.Biomedicines · 2016Article
- Towards a Safer, More Randomized Lentiviral Vector Integration Profile Exploring Artificial LEDGF Chimeras.PloS one · 2016Article
- Sites of retroviral DNA integration: From basic research to clinical applications.Critical reviews in biochemistry and molecular biology · 2016Review
- Retroviral integration: Site matters: Mechanisms and consequences of retroviral integration site selection.BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Review
- Host Factors in Retroviral Integration and the Selection of Integration Target Sites.Microbiology spectrum · 2014Review
- Allosteric inhibition of human immunodeficiency virus integrase: late block during viral replication and abnormal multimerization involving specific protein domains.The Journal of biological chemistry · 2014Article
- Efficient Transduction of LEDGF/p75 Mutant Cells by Gain-of-Function HIV-1 Integrase Mutant Viruses.Molecular therapy. Methods & clinical development · 2014Article
- Molecular mechanisms of retroviral integration site selection.Nucleic acids research · 2014Article
- Bromo- and extraterminal domain chromatin regulators serve as cofactors for murine leukemia virus integration.Journal of virology · 2013Article
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 1 institution in 1 country.
Funding
Abstract
HIV-1-based lentiviral vectors are a promising tool for gene therapy. However, integration of a lentiviral vector into host cell genes may lead to the development of cancer. Therefore, control of integration site selection is critical to the successful outcome of gene therapy approaches that use these vectors. The discovery that integration site selection by HIV-1 and HIV-1-based vectors is controlled by the LEDGF/p75 protein has presented new opportunities to control integration site selection. In this study, we tested the hypothesis that a fusion protein containing the C-terminal HIV integrase-binding portion of LEDGF/p75, and the N-terminal chromodomain of heterochromatin protein-1alpha (HP1alpha), can target HIV-1 vector DNA outside of genes. We show that this fusion protein, termed TIHPLE, associates with the heterochromatin hallmark trimethylated Lys-9 of histone H3 (H3K9me3). Transient overexpression of TIHPLE alters integration site selection by an HIV-1-based vector and decreases the number of integration events that occur in genes. This change in integration site selection was achieved without a reduction in overall integration efficiency. Furthermore, we show that TIHPLE increases integration in the vicinity of H3K9me3 and in repetitive DNA sequences. These data provide a novel approach to address the problem of the tendency of retroviral vectors to integrate at undesirable sites of the human genome.
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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.