title: Efficient gene transfer to airway epithelium using recombinant Sendai virus.
abstract: Clinical 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.
authors.affiliation: Department of Gene Therapy, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Yonemitsu
authors.forename: C
authors.initials: C
authors.lastname: Kitson
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: R
authors.initials: R
authors.lastname: Farley
authors.forename: U
authors.initials: U
authors.lastname: Griesenbach
authors.forename: D
authors.initials: D
authors.lastname: Judd
authors.forename: R
authors.initials: R
authors.lastname: Steel
authors.forename: P
authors.initials: P
authors.lastname: Scheid
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: P K
authors.initials: PK
authors.lastname: Jeffery
authors.forename: A
authors.initials: A
authors.lastname: Kato
authors.forename: M K
authors.initials: MK
authors.lastname: Hasan
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
authors.forename: I
authors.initials: I
authors.lastname: Masaki
authors.forename: M
authors.initials: M
authors.lastname: Fukumura
authors.forename: M
authors.initials: M
authors.lastname: Hasegawa
authors.forename: D M
authors.initials: DM
authors.lastname: Geddes
authors.forename: E W
authors.initials: EW
authors.lastname: Alton
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001980:Bronchi / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000628:therapy; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005289:Ferrets; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018108:Respirovirus / Q000235:genetics*; D012756:Sheep; D013997:Time Factors; D014132:Trachea / Q000378:metabolism*; D014162:Transfection
chemical_list: D008081:Liposomes; D011956:Receptors, Cell Surface; C092488:sialic acid receptor; D008156:Luciferases