ArticleGene therapy2013
Efficient in vivo regulation of cytidine deaminase expression in the haematopoietic system using a doxycycline-inducible lentiviral vector system.
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 10 papers.
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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.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- The Emerging Role of Cytidine Deaminase in Human Diseases: A New Opportunity for Therapy?Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- The CpG-sites of the CBX3 ubiquitous chromatin opening element are critical structural determinants for the anti-silencing function.Scientific reports · 2017Article
- Chemoprotection of murine hematopoietic cells by combined gene transfer of cytidine deaminase (CDD) and multidrug resistance 1 gene (MDR1).Journal of experimental & clinical cancer research : CR · 2015Article
- Tightly regulated 'all-in-one' lentiviral vectors for protection of human hematopoietic cells from anticancer chemotherapy.Gene therapy · 2015Article
- Deoxycytidine-kinase knockdown as a novel myeloprotective strategy in the context of fludarabine, cytarabine or cladribine therapy.Leukemia · 2015Article
- Induced neural stem/precursor cells for fundamental studies and potential application in neurodegenerative diseases.Neuroscience bulletin · 2015Review
- R88-APOBEC3Gm Inhibits the Replication of Both Drug-resistant Strains of HIV-1 and Viruses Produced From Latently Infected Cells.Molecular therapy. Nucleic acids · 2014Article
- Myeloprotection by cytidine deaminase gene transfer in antileukemic therapy.Neoplasia (New York, N.Y.) · 2013Review
- Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice.PLoS pathogens · 2013Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated transgene expression may reduce transgene-specific and genotoxic risks associated with gene therapy. To prove this concept, we have investigated the suitability of doxycycline (Dox)-inducible human cytidine deaminase (hCDD) overexpression from lentiviral vectors to mediate effective myeloprotection while circumventing the lymphotoxicity observed with constitutive CDD activity. Rapid Dox-mediated transgene induction associated with a 6-17-fold increase in drug resistance was observed in 32D and primary murine bone marrow (BM) cells. Moreover, robust Dox-regulated transgene expression in the entire haematopoietic system was demonstrated for primary and secondary recipients of hCDD-transduced R26-M2rtTA transgenic BM cells. Furthermore, mice were significantly protected from myelosuppressive chemotherapy as evidenced by accelerated recovery of granulocytes (1.9±0.6 vs 1.3±0.3, P=0.034) and platelets (883±194 vs 584±160 10(3) per μl, P=0.011). Minimal transgene expression in the non-induced state and no overt cellular toxicities including lymphotoxicity were detected. Thus, using a relevant murine transplant model our data provide conclusive evidence that drug-resistance transgenes can be expressed in a regulated fashion in the lymphohaematopoietic system, and that Dox-inducible systems may be used to reduce myelotoxic side effect of anticancer chemotherapy or to avoid side effects of high constitutive transgene expression.
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