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Efficient nonviral gene therapy with FasL and Del1 fragments in mice
Author(s) -
Kitano Hisataka,
Mamiya Atsushi,
Kokubun Shinichiro,
Hidai Chiaki
Publication year - 2012
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.2682
Subject(s) - genetic enhancement , transfection , fas ligand , gene delivery , electroporation , stromal cell , cancer research , plasmid , viral vector , biology , apoptosis , fusion gene , fusion protein , microbiology and biotechnology , cell culture , gene , medicine , immunology , programmed cell death , genetics , recombinant dna
Background The 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 the use of highly efficient viral vectors. However, because viral vector‐based gene therapy is associated with certain risks, the development of effective nonviral routes for gene delivery would be useful. The present study aimed to improve FasL gene therapy with a nonviral 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, Jet‐PEI (PolyPlus‐transfection, San Marcos, CA, USA). Results All mice treated with a negative control plasmid or pFasL died within 49 days. By 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 obtained in the present study suggest that the protein deposition‐based approach described, which makes use of the E3 and C1 domains of Del1, could comprise a novel method for cancer gene therapy with nonviral vectors. Copyright © 2012 John Wiley & Sons, Ltd.