| Efficient non-viral gene therapy with FasL and Del1 fragments in mice. | |
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MedLine Citation:
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PMID: 23136083 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Expression of FasL in cancer cells is currently being explored as a potential cancer therapy. Because high levels of FasL are necessary for effective treatment, current methods typically rely on use of highly efficient viral vectors. However, because viral vector-based gene therapy is associated with certain risks, the development of effective non-viral routes for gene delivery would be useful. The aim of this study is to improve FasL gene therapy with a non-viral vector by taking advantage of the E3 and C1 domains of Del1 protein, which induces apoptosis and localizes to the extracellular matrix. METHODS: Mouse explanted tumors derived from a human oral squamous cell carcinoma cell line, SCCKN, were treated with plasmids encoding FasL (pFasL), E3C1 (pE3C1), and a fusion of FasL and E3C1 (pFasL-E3C1). The plasmids were injected locally every 7 days along with a transfection reagent, jetPEI. RESULTS: All mice treated with a negative control plasmid or pFasL died within 49 days. In contrast, 83% of mice treated with pFasL-E3C1 survived longer than 49 days. Histochemical studies revealed that the fusion protein is localized to the stroma and induces apoptosis in stromal cells and adjacent parenchymal cells. CONCLUSIONS: The results suggest that the protein deposition-based approach we describe, which makes use of the E3 and C1 domains of Del1, could be a novel method for cancer gene therapy with non-viral vectors. Copyright © 2012 John Wiley & Sons, Ltd. |
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Authors:
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Hisataka Kitano; Atsushi Mamiya; Shinichiro Kokubun; Chiaki Hidai |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-8 |
Journal Detail:
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Title: The journal of gene medicine Volume: - ISSN: 1521-2254 ISO Abbreviation: J Gene Med Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815764 Medline TA: J Gene Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 John Wiley & Sons, Ltd. |
Affiliation:
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Division of Dental Surgery, Nihon University School of Medicine, Tokyo, 173-8610, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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