title: Sendai virus transgene in a novel gene therapy for laryngotracheal disease.
abstract: OBJECTIVE
  Vocal cord scar formation and laryngotracheal stenosis (LTS) are challenging problems for otolaryngologists. Sendai virus (SeV) vectors have been shown to transduce airway epithelium efficiently, and are thus ideal for modulating airway wound-healing therapy. To assess the potential utility of SeV gene therapy for laryngotracheal diseases, we established a novel LTS model and examined the transduction efficiency of SeV vectors in normal and LTS model tissue.
  
  
  METHODS
  Basic science.
  
  
  METHODS
  Fusion (F) gene-deleted, nontransmissible SeV vectors were used. First, the route dependency and transduction efficiency of SeV vectors for normal mucosa in the larynx were examined. Next, the novel LTS rat model was established and evaluated. Finally, the transduction efficiency of SeV vectors in injured mucosa of the LTS model was evaluated.
  
  
  RESULTS
  Simple spray delivery of the SeV vector resulted in significant and persistent expression of the reporter gene in normal laryngotracheal epithelium. Transgenic SeV-mediated expression was maximal at 3 days, decreased over time, but remained detectable for 14 days after administration. No serious side effects were observed in the larynx or trachea. The model achieved an average of 60% tracheal stenosis in the cross-sectional area. Efficient SeV-mediated transgene expression was observed in the injured mucosa at the levels of the trachea, cricoid cartilage, and vocal cord.
  
  
  CONCLUSIONS
  A novel animal model for LTS was established. We successfully demonstrated SeV-mediated transgene expression in normal tissue and in the injured mucosa of the LTS model. SeV might be a promising strategy for gene therapy in laryngotracheal diseases.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mizokami
authors.forename: Koji
authors.initials: K
authors.lastname: Araki
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tomifuji
authors.forename: Taku
authors.initials: T
authors.lastname: Yamashita
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shiotani
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D029082:Sendai virus / Q000235:genetics*; D014135:Tracheal Stenosis / Q000628:therapy*; D014161:Transduction, Genetic; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase