- Paper Report
- Open Access
Novel vector improves efficiency of gene transfer to the airway epithelium
- Raymond Pickles1
© Biomed Central Ltd 2001
- Received: 21 December 2000
- Accepted: 18 September 2001
- Published: 18 September 2001
- gene therapy
Gene therapy strategies for the treatment of cystic fibrosis (CF) lung disease have been hindered by the low gene transfer efficiency with which currently available vectors (eg adenovirus, liposomes, retrovirus) deliver transgenes to the airway epithelium in vivo. This inefficiency is mainly due to the inability of lumenally delivered vectors to attach to and enter the epithelial cells that line the airways, which in turn reflects the lack of the necessary vector receptors at the lumenal surface. This study describes the use of a new vector type, the Sendai virus (SeV), which displays high efficiency gene transfer in a number of experimental airway models and suggests that this vector may be useful for gene delivery to the lung.
The efficiencies with which SeV vectors can deliver transgenes to airway cells was compared with adenoviral and liposomal vectors. These vectors were tested in a number of models of respiratory airway epithelial cells: freshly isolated human nasal epithelial cells and excised sheep airway epithelium in vitro, and murine and ferret airways in vivo. The authors report that SeV produced 3-4 logs greater gene transfer efficiencies to the epithelial cells in all the models tested when compared to adenoviral and liposomal vectors. In fact, in vivo, the authors show data demonstrating that 70-80% of airway epithelial cells express transgenes, an efficiency that surpasses any previously reported studies with viral vectors in the large airways of in vivo models. Furthermore, the authors show that the airway mucus barrier does not impede vector access to the cells, and that, in contrast to other vectors, the exposure time of SeV to the epithelium can be brief. In addition, although limited, the study attempts to describe the airway inflammation caused by administration of this vector.
Gene transfer, recombinant vectors, airway epithelium models
- Yonemitsu Y, Kitson C, Ferrari S, Farley R, Griesenbach U, Judd D, Steel R, Scheid P, Zhu J, Jeffrey P, Kato A, Hasan M, Nagai Y, Masaki I, Fukumura M, Geddes D, Alton E: Efficient gene transfer to airway epithelium using recombinant Sendai virus. Nat Biotechnol . 2000, 18: 970-973.View ArticleGoogle Scholar