ArticleHuman gene therapy2012
Integrase-deficient lentiviral vectors mediate efficient gene transfer to human vascular smooth muscle cells with minimal genotoxic risk.
Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Targeted knock-in ofMolecular therapy. Nucleic acids · 2024Article
- Integrated analysis of tRNA-derived small RNAs in proliferative human aortic smooth muscle cells.Cellular & molecular biology letters · 2022Article
- VSV-G-Enveloped Vesicles for Traceless Delivery of CRISPR-Cas9.Molecular therapy. Nucleic acids · 2018Article
- Viral and Nonviral Engineering of Natural Killer Cells as Emerging Adoptive Cancer Immunotherapies.Journal of immunology research · 2018Review
- Hit and go CAS9 delivered through a lentiviral based self-limiting circuit.Nature communications · 2017Article
- The inflammatory protein Pentraxin 3 in cardiovascular disease.Immunity & ageing : I & A · 2016Review
- Nogo-B protects mice against lipopolysaccharide-induced acute lung injury.Scientific reports · 2015Article
- Highly efficient in vitro and in vivo delivery of functional RNAs using new versatile MS2-chimeric retrovirus-like particles.Molecular therapy. Methods & clinical development · 2015Article
- Generation of a stable packaging cell line producing high-titer PPT-deleted integration-deficient lentiviral vectors.Molecular therapy. Methods & clinical development · 2015Article
- Transgenic expression of human glial cell line-derived neurotrophic factor from integration-deficient lentiviral vectors is neuroprotective in a rodent model of Parkinson's disease.Human gene therapy · 2014Article
- Integration-deficient lentiviral vectors expressing codon-optimized R338L human FIX restore normal hemostasis in Hemophilia B mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
We have previously shown that injury-induced neointima formation was rescued by adenoviral-Nogo-B gene delivery. Integrase-competent lentiviral vectors (ICLV) are efficient at gene delivery to vascular cells but present a risk of insertional mutagenesis. Conversely, integrase-deficient lentiviral vectors (IDLV) offer additional benefits through reduced mutagenesis risk, but this has not been evaluated in the context of vascular gene transfer. Here, we have investigated the performance and genetic safety of both counterparts in primary human vascular smooth muscle cells (VSMC) and compared gene transfer efficiency and assessed the genotoxic potential of ICLVs and IDLVs based on their integration frequency and insertional profile in the human genome. Expression of enhanced green fluorescent protein (eGFP) mediated by IDLVs (IDLV-eGFP) demonstrated efficient transgene expression in VSMCs. IDLV gene transfer of Nogo-B mediated efficient overexpression of Nogo-B in VSMCs, leading to phenotypic effects on VSMC migration and proliferation, similar to its ICLV version and unlike its eGFP control and uninfected VSMCs. Large-scale integration site analyses in VSMCs indicated that IDLV-mediated gene transfer gave rise to a very low frequency of genomic integration compared to ICLVs, revealing a close-to-random genomic distribution in VSMCs. This study demonstrates for the first time the potential of IDLVs for safe and efficient vascular gene transfer.
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