ArticleMolecular therapy. Nucleic acids2014
BET-independent MLV-based Vectors Target Away From Promoters and Regulatory Elements.
Article in Molecular therapy. Nucleic acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting.Viruses · 2024Article
- Advances in HIV Gene Therapy.International journal of molecular sciences · 2024Review
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- Interaction modules that impart specificity to disordered protein.Trends in biochemical sciences · 2023Review
- Pseudotyped Viruses.Advances in experimental medicine and biology · 2023Article
- Review
- BET-Independent Murine Leukemia Virus Integration Is RetargetedMicrobiology spectrum · 2022Article
- Multivalent interactions essential for lentiviral integrase function.Nature communications · 2022Article
- Improved functionality and potency of next generation BinMLV viral vectors toward safer gene therapy.Molecular therapy. Methods & clinical development · 2021Article
- Predicting genotoxicity of viral vectors for stem cell gene therapy using gene expression-based machine learning.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Retroviral gene therapy in Germany with a view on previous experience and future perspectives.Gene therapy · 2021Review
- Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges.Frontiers in molecular biosciences · 2021Review
- Disrupting MLV integrase:BET protein interaction biases integration into quiescent chromatin and delays but does not eliminate tumor activation in a MYC/Runx2 mouse model.PLoS pathogens · 2019Article
- Shifting Retroviral Vector Integrations Away from Transcriptional Start Sites via DNA-Binding Protein Domain Insertion into Integrase.Molecular therapy. Methods & clinical development · 2019Article
- Post-mitotic BET-induced reshaping of integrase quaternary structure supports wild-type MLV integration.Nucleic acids research · 2019Article
- Murine leukemia virus p12 tethers the capsid-containing pre-integration complex to chromatin by binding directly to host nucleosomes in mitosis.PLoS pathogens · 2018Article
- Article
- Engineering Next-Generation BET-Independent MLV Vectors for Safer Gene Therapy.Molecular therapy. Nucleic acids · 2017Article
- Integration site selection by retroviruses and transposable elements in eukaryotes.Nature reviews. Genetics · 2017Review
- The FACT Complex Promotes Avian Leukosis Virus DNA Integration.Journal of virology · 2017Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stable integration in the host genome renders murine leukemia virus (MLV)-derived vectors attractive tools for gene therapy. Adverse events in otherwise successful clinical trials caused by proto-oncogene activation due to vector integration hamper their application. MLV and MLV-based vectors integrate near strong enhancers, active promoters, and transcription start sites (TSS) through specific interaction of MLV integrase (IN) with the bromodomain and extra-terminal (BET) family of proteins, accounting for insertional mutagenesis. We identified a BET-interaction motif in the C-terminal tail of MLV IN conserved among gammaretroviruses. By deletion of this motif or a single point mutation (INW390A), BET-independent MLV (BinMLV) were engineered. BinMLV vectors carrying INW390A integrate at wild-type efficiency, with an integration profile that no longer correlates with BET chromatin distribution nor with the traditional markers of MLV integration. In particular, BinMLV vector integration associated less with oncogene TSS compared to the MLV vectors currently used in clinical trials. Together, these findings open perspectives to increase the biosafety of gammaretroviral vectors for gene therapy.
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.