ArticleThe Journal of clinical investigation2012
Whole transcriptome characterization of aberrant splicing events induced by lentiviral vector integrations.
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 73 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
73 citing papers in PubMed.
- Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency.Nature communications · 2022Trial
- When RNA goes off script: ensuring transcript fidelity in transgene expression.The EMBO journal · 2026Review
- Dual AAV vectors for efficient delivery of large transgenes.Nature protocols · 2026Review
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- Article
- Neonatal gene therapy effectively prevents disease manifestations in a murine model of Mucopolysaccharidosis type I.Molecular therapy. Methods & clinical development · 2025Article
- Preclinical development of lentiviral vector gene therapy for Diamond-Blackfan anemia syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Balancing efficacy and safety in lentiviral vector-mediated hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Optimization of a lentivirus-mediated gene therapy targeting HIV-1 RNA to eliminate HIV-1-infected cells.Molecular therapy. Nucleic acids · 2024Article
- Mechanisms and Delivery of tRNA Therapeutics.Chemical reviews · 2024Review
- Article
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- Editorial: The relevance of molecular mechanisms in HIV-1 latency and reactivation from latency.Frontiers in cellular and infection microbiology · 2023Article
- Review
- Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Aberrant splicing events caused by insertion of genes of interest into expression vectors.International journal of biological sciences · 2022Article
- CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells.Frontiers in immunology · 2022Article
- Detection of Chimeric Cellular: HIV mRNAs Generated Through Aberrant Splicing in HIV-1 Latently Infected Resting CD4+ T Cells.Frontiers in cellular and infection microbiology · 2022Article
- Overexpression of lncRNAs with endogenous lengths and functions using a lncRNA delivery system based on transposon.Journal of nanobiotechnology · 2021Article
- Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Gamma-retroviral/lentiviral vectors (γRV/LV) with self-inactivating (SIN) long terminal repeats (LTRs) and internal moderate cellular promoters pose a reduced risk of insertional mutagenesis when compared with vectors with active LTRs. Yet, in a recent LV-based clinical trial for β-thalassemia, vector integration within the HMGA2 gene induced the formation of an aberrantly spliced mRNA form that appeared to cause clonal dominance. Using a method that we developed, cDNA linear amplification-mediated PCR, in combination with high-throughput sequencing, we conducted a whole transcriptome analysis of chimeric LV-cellular fusion transcripts in transduced human lymphoblastoid cells and primary hematopoietic stem/progenitor cells. We observed a surprising abundance of read-through transcription originating outside and inside the provirus and identified the vector sequences contributing to the aberrant splicing process. We found that SIN LV has a sharply reduced propensity to engage in aberrant splicing compared with that of vectors carrying active LTRs. Moreover, by recoding the identified vector splice sites, we reduced residual read-through transcription and demonstrated an effective strategy for improving vectors. Characterization of the mechanisms and genetic features underlying vector-induced aberrant splicing will enable the generation of safer vectors, with low impact on the cellular transcriptome.
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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.