title: The nasal epithelium as a factory for systemic protein delivery.
abstract: We have previously shown that recombinant Sendai virus (SeV) produces efficient in vivo airway epithelial gene transfer. The ability to produce therapeutic levels of circulating proteins following noninvasive gene transfer would have widespread clinical application. Here, we compared nose, lung, and skeletal muscle for the ability to produce circulating levels of the secreted mouse antiinflammatory cytokine interleukin-10 (IL10) following SeV-mediated gene transfer. High levels of serum IL10 were obtained from each site with a potency order of lung > nose > muscle for a given viral titer. Serum levels from each site were within the likely required range for anti-inflammatory effects. The combination of a high-efficiency gene transfer agent (SeV) and sites that can be assessed noninvasively (nose or lung) may circumvent several current challenges to gene therapy.
authors.affiliation: Department of Gene Therapy, Imperial College School of Medicine at the National Heart and Lung Institute, London, SM5 1RU, UK. u.griesenbach@ic.ac.uk
authors.forename: Uta
authors.initials: U
authors.lastname: Griesenbach
authors.forename: Robin L
authors.initials: RL
authors.lastname: Cassady
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fukumura
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jeffery
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nagai
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Geddes
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Eric W F W
authors.initials: EW
authors.lastname: Alton
mesh_terms: D000818:Animals; D019556:COS Cells; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000235:genetics; D008168:Lung / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism*; D029082:Sendai virus / Q000235:genetics*
chemical_list: D016753:Interleukin-10