ArticleThe Journal of clinical investigation2012
Lentiviral vector integration in the human genome induces alternative splicing and generates aberrant transcripts.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 176 citations in OpenAlex.
- Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency.Nature communications · 2022Trial
- Long Term Follow Up of Hereditary Thrombotic Thrombocytopenic Purpura on Plasma Therapy for 9 Years: A Case Report.Clinical case reports · 2026Article
- Targeted KEAP1 disruption enhances antioxidant defense and mesenchymal stromal cell therapy for chronic limb-threatening ischemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.bioRxiv : the preprint server for biology · 2026Article
- When RNA goes off script: ensuring transcript fidelity in transgene expression.The EMBO journal · 2026Review
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- Adaptation of lentiviral vectors for viral gene therapy and their impact on host cell biology.Journal of translational medicine · 2026Review
- Delivery platforms forFrontiers in immunology · 2026Review
- In vivo chemogenetic RNA editing of macrophages by bioengineered viruses for sepsis treatment.Nature communications · 2025Article
- Long Non-coding RNA Based Therapy for Cardiovascular Disease.Journal of cardiovascular translational research · 2025Review
- CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization.Cell communication and signaling : CCS · 2025Review
- Neonatal gene therapy effectively prevents disease manifestations in a murine model of Mucopolysaccharidosis type I.Molecular therapy. Methods & clinical development · 2025Article
- Transduction of Lentiviral Vectors andInternational journal of molecular sciences · 2025Article
- Exploring precision treatments in immune-mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery.Exploration (Beijing, China) · 2025Review
- Optimization of a lentivirus-mediated gene therapy targeting HIV-1 RNA to eliminate HIV-1-infected cells.Molecular therapy. Nucleic acids · 2024Article
- Development of artificial transcription factors and their applications in cell reprograming, genetic screen, and disease treatment.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Stable inhibition of choroidal neovascularization by adeno-associated virus 2/8-vectored bispecific molecules.Gene therapy · 2024Article
- The Current Landscape of Secondary Malignancies after CAR T-Cell Therapies: How Could Malignancies Be Prevented?International journal of molecular sciences · 2024Review
- The Complex Dysregulations of CD4 T Cell Subtypes in HIV Infection.International journal of molecular sciences · 2024Review
- Novel mechanisms of action of emerging therapies of hereditary thrombotic thrombocytopenic purpura.Expert review of hematology · 2024Review
45 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Retroviral vectors integrate in genes and regulatory elements and may cause transcriptional deregulation of gene expression in target cells. Integration into transcribed genes also has the potential to deregulate gene expression at the posttranscriptional level by interfering with splicing and polyadenylation of primary transcripts. To examine the impact of retroviral vector integration on transcript splicing, we transduced primary human cells or cultured cells with HIV-derived vectors carrying a reporter gene or a human β-globin gene under the control of a reduced-size locus-control region (LCR). Cells were randomly cloned and integration sites were determined in individual clones. We identified aberrantly spliced, chimeric transcripts in more than half of the targeted genes in all cell types. Chimeric transcripts were generated through the use of constitutive and cryptic splice sites in the HIV 5ι long terminal repeat and gag gene as well as in the β-globin gene and LCR. Compared with constitutively spliced transcripts, most aberrant transcripts accumulated at a low level, at least in part as a consequence of nonsense-mediated mRNA degradation. A limited set of cryptic splice sites caused the majority of aberrant splicing events, providing a strategy for recoding lentiviral vector backbones and transgenes to reduce their potential posttranscriptional genotoxicity.
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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.