OBJECTIVES/HYPOTHESIS: 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. STUDY DESIGN: 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. CONCLUSION: 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.
OBJECTIVES/HYPOTHESIS: 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. STUDY DESIGN: 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. CONCLUSION: 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: N Tanaka; K Araki; D Mizokami; Y Miyagawa; T Yamashita; M Tomifuji; Y Ueda; M Inoue; K Matsushita; F Nomura; H Shimada; A Shiotani Journal: Gene Ther Date: 2015-01-15 Impact factor: 5.250