title: Efficient nonviral gene therapy with FasL and Del1 fragments in mice.
abstract: 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.
authors.affiliation: Division of Dental Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kitano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mamiya
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kokubun
authors.forename: Chiaki
authors.initials: C
authors.lastname: Hidai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002135:Calcium-Binding Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D036341:Intercellular Signaling Peptides and Proteins