ArticleGene therapy2013
Self-inactivating MLV vectors have a reduced genotoxic profile in human epidermal keratinocytes.
Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The Era of Gene Therapy: The Advancement of Lentiviral Vectors and Their Pseudotyping.Viruses · 2025Review
- A cellular disease model toward gene therapy ofMolecular therapy. Methods & clinical development · 2024Article
- Optimal delivery of RNA interference by viral vectors for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis.Nucleic acids research · 2021Article
- Delivery technologies for in utero gene therapy.Advanced drug delivery reviews · 2021Review
- Hologene 5: A Phase II/III Clinical Trial of Combined Cell and Gene Therapy of Junctional Epidermolysis Bullosa.Frontiers in genetics · 2021Article
- Genome-edited adult stem cells: Next-generation advanced therapy medicinal products.Stem cells translational medicine · 2020Review
- 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
- Article
- An RNA-targeted therapy for dystrophic epidermolysis bullosa.Nucleic acids research · 2017Article
- Simple viral/minimal piggyBac hybrid vectors for stable production of self-inactivating gamma-retroviruses.BMC research notes · 2015Article
- Coherence analysis discriminates between retroviral integration patterns in CD34(+) cells transduced under differing clinical trial conditions.Molecular therapy. Methods & clinical development · 2015Article
- Genome-wide analysis of alpharetroviral integration in human hematopoietic stem/progenitor cells.Genes · 2014Article
- Article
- Molecular mechanisms of retroviral integration site selection.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transplantation of epithelia derived from keratinocyte stem cells transduced by retroviral vectors is a potential therapy for epidermolysis bullosa (EB), a family of inherited skin adhesion defects. The biosafety characteristics of retroviral vectors in keratinocytes are, however, poorly defined. We developed self-inactivating (SIN) vectors derived from the Moloney murine leukemia (MLV) and the human immunodeficiency (HIV) viruses expressing therapeutic levels of LAMB3, a transgene defective in junctional EB, and tested their integration profile in human primary keratinocytes. The SIN-HIV vector showed the expected preference for transcribed genes while the SIN-MLV vector integrated preferentially in regulatory elements, but showed a significantly lower tendency to target cell growth-related genes, transcription start sites and epigenetically defined promoters compared with a wild-type MLV vector in an epithelial cell context. A quantitative gene expression assay in individual keratinocyte clones showed that MLV-derived vectors deregulate expression of targeted genes at a lower frequency than in hematopoietic cells, and that the SIN-MLV design has the lowest activity compared to both MLV and SIN-HIV vectors. This study indicates that SIN-MLV vectors may have a better safety profile in keratinocyte than in hematopoietic cells, and be a reasonable alternative to lentiviral vectors for gene therapy of inherited skin disorders.
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Registered trials
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