センダイウイルスベクターによる気管狭窄の遺伝子治療

DOI Web Site 参考文献31件 オープンアクセス

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  • Gene Therapy for Tracheal Stenosis Using Sendai Virus Vector

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Acquired tracheal stenosis remains a challenging problem for otolaryngologists. The objective of this study was to determine whether the Sendai virus(SeV)-mediated c-myc suppressor, a far upstream element(FUSE)-binding protein(FBP)-interacting repressor(FIR), modulates wound healing of the airway mucosa, and whether it prevents tracheal stenosis in an animal model of induced mucosal injury. First, a novel animal model for LTS was established. Next, we successfully demonstrated SeV-mediated transgene expression in the injured mucosa of the LTS model. Finally, a fusion gene-deleted, non-transmissible SeV vector encoding FIR(FIR-SeV/ΔF)was prepared. FIR-SeV/ΔF was administered to the rats with scraped airway mucosae through the tracheostoma. Untreated animals showed hyperplasia of the airway epithelium and a thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition causing lumen stenosis. In contrast, the administration of FIR-SeV/ΔF decreased the degree of tracheal stenosis and improved the survival rate. Immunohistochemical staining showed that c-Myc expression was downregulated in the tracheal basal cells of the FIRSeV/ΔF-treated animals, suggesting that c-myc was suppressed by FIR-SeV/ΔF in the regenerating airway epithelium of the injured tracheal mucosa. The airway-targeted gene therapy of the c-myc suppressor FIR, using a recombinant SeV vector, prevented tracheal stenosis in a rat model of airway mucosal injury.

収録刊行物

  • 喉頭

    喉頭 27 (2), 51-58, 2015

    日本喉頭科学会

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