Document Detail


Efficient non-viral gene therapy with FasL and Del1 fragments in mice.
MedLine Citation:
PMID:  23136083     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Hisataka Kitano; Atsushi Mamiya; Shinichiro Kokubun; Chiaki Hidai
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  The journal of gene medicine     Volume:  -     ISSN:  1521-2254     ISO Abbreviation:  J Gene Med     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815764     Medline TA:  J Gene Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
Affiliation:
Division of Dental Surgery, Nihon University School of Medicine, Tokyo, 173-8610, Japan.
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