The nasal epithelium as a factory for systemic protein delivery.

Griesenbach U, Cassady RL, Ferrari S, Fukumura M, Müller C, Schmitt E, Zhu J, Jeffery PK, Nagai Y, Geddes DM, Hasegawa M, Alton EW

Molecular Therapy : The Journal Of The American Society Of Gene Therapy

Mol Ther. 2002 Feb;5(2):98-103.

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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.

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