Nature Biotechnology
18, 970 - 973 (2000)
doi:10.1038/79463
Efficient gene transfer to airway epithelium using recombinant Sendai virusYoshikazu Yonemitsu1, Christopher Kitson1, Stefano Ferrari1, Raymond Farley1, Uta Griesenbach1, Diane Judd1, Rachel Steel1, Philippe Scheid1, Jie Zhu1, Peter K. Jeffery1, Atsushi Kato2, Mohammad K. Hasan2, Yoshiyuki Nagai3, Ichiro Masaki4, Masayuki Fukumura5, Mamoru Hasegawa5, Duncan M. Geddes1
& Eric W.F.W. Alton11
Department of Gene Therapy, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK. 2
Department of Viral Infection and Vaccine Control, National Institute for Infectious Diseases, Tokyo, Japan. 3
AIDS Research Centre, National Institute for Infectious Diseases, Tokyo, Japan
4
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 5
DNAVEC Research Inc., Tsukuba-city, Ibaraki, Japan.
Correspondence should be addressed to Eric W.F.W. Alton e.alton@ic.ac.ukSendai viruscystic fibrosisgene therapyClinical studies of gene therapy for cystic fibrosis (CF) suggest that the key problem is the efficiency of gene transfer to the airway epithelium. The availability of relevant vector receptors, the transient contact time between vector and epithelium, and the barrier function of airway mucus contribute significantly to this problem. We have recently developed recombinant Sendai virus (SeV) as a new gene transfer agent. Here we show that SeV produces efficient transfection throughout the respiratory tract of both mice and ferrets in vivo, as well as in freshly obtained human nasal epithelial cells in vitro. Gene transfer efficiency was several log orders greater than with cationic liposomes or adenovirus. Even very brief contact time was sufficient to produce this effect, and levels of expression were not significantly reduced by airway mucus. Our investigations suggest that SeV may provide a useful new vector for airway gene transfer.
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