Presented at the American Laryngological Association's Spring Meeting on April 28, 2011, in Chicago, Illinois, and on April 19, 2012, in San Diego, California, U.S.A.
Sendai virus transgene in a novel gene therapy for laryngotracheal disease
Article first published online: 10 MAY 2013
Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 123, Issue 7, pages 1717–1724, July 2013
How to Cite
Mizokami, D., Araki, K., Tanaka, N., Suzuki, H., Tomifuji, M., Yamashita, T., Inoue, M., Hasegawa, M. and Shiotani, A. (2013), Sendai virus transgene in a novel gene therapy for laryngotracheal disease. The Laryngoscope, 123: 1717–1724. doi: 10.1002/lary.23917
This work was supported by grants from the National Defense Medical College Special Research Grant, Research Promotion-Grant on Defense Medicine, and Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No.23592545). The authors have no other funding, financial relationships, or conflicts of interest to disclose.
- Issue published online: 24 JUN 2013
- Article first published online: 10 MAY 2013
- Manuscript Accepted: 5 NOV 2012
- Sendai virus;
- gene therapy;
- tracheal stenosis;
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.
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.
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.
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.
Level of Evidence